Short stature in small-for-gestational-age offspring born to mothers with hypertensive disorders of pregnancy.

OBJECTIVE: To investigate the incidence and risk factors of small-for-gestational age (SGA) short stature at 2 and 3 years of age in SGA offspring born to women with hypertensive disorders of pregnancy (HDP). METHODS: We examined 226 women with HDP whose respective SGA offspring were delivered. RESULTS: Eighty offspring (41.2%) were diagnosed with SGA short stature. The prematurity before 32 weeks of gestation was the most significant factor for catch-up growth failure. CONCLUSION: In SGA offspring born to women with HDP, SGA short stature incidence was high, and the risk factor was prematurity before 32 weeks of gestation.

Predicting the risk of fetal growth restriction by radiomics analysis of the placenta on T2WI: A retrospective case-control study.

INTRODUCTION: Fetal growth restriction (FGR) is associated with placental abnormalities, and its precise diagnosis is challenging. This study aimed to explore the role of radiomics based on placental MRI in predicting FGR. METHODS: A retrospective study using T2-weighted placental MRI data were conducted. A total of 960 radiomic features were automatically extracted. Features were selected using three-step machine learning methods. A combined model was constructed by combining MRI-based radiomic features and ultrasound-based fetal measurements. The receiver operating characteristic curves (ROC) were conducted to assess model performance. Additionally, decision curves and calibration curves were performed to evaluate prediction consistency of different models. RESULTS: Among the study participants, pregnant women who delivered from January 2015 to June 2021 were randomly divided into training (n = 119) and test (n = 40) sets. Forty-three other pregnant women who delivered from July 2021 to December 2021 were used as the time-independent validation set. After training and testing, three radiomic features that were strongly correlated with FGR were selected. The area under the ROC curves (AUCs) of the MRI-based radiomics model reached 0.87 (95% confidence interval [CI]: 0.74-0.96) and 0.87 (95% CI: 0.76-0.97) in the test and validation sets, respectively. Moreover, the AUCs for the model comprising MRI-based radiomic features and ultrasound-based measurements were 0.91 (95% CI: 0.83-0.97) and 0.94 (95% CI: 0.86-0.99) in the test and validation sets, respectively. DISCUSSION: MRI-based placental radiomics could accurately predict FGR. Moreover, combining placental MRI-based radiomic features with ultrasound indicators of the fetus could improve the diagnostic accuracy of FGR.

Investigating protein C and S levels in pregnant women with recurrent early pregnancy loss versus normal pregnancy.

Miscarriage in the first and second trimesters of pregnancy is very common, and coagulopathy can be a contributing factor. Protein C and S deficiency are rare, inherited disorders that can increase the risk of thrombophilia. Women with these deficiencies have a higher risk of developing blood clots in the placenta, which can lead to placental insufficiency and, ultimately, to a miscarriage. We aimed to compare the levels of protein C and protein S in pregnant females with recurrent first and second-trimester pregnancy loss and normal pregnant females. We performed a detailed history, examination, and various lab tests on a cohort of 40 females with a history of recurrent first and second-trimester abortions visiting an outpatient clinic at a multi-specialty hospital in Kashmir, India. All the findings were compared with 40 women with normal pregnancies. 10% of the participants had low protein C and S levels (P=0.277), out of whom 75% (p<0.001) had intrauterine growth retardation (IUGR) on ultrasound with 67% (p<0.001) having reduced doppler flow in the umbilical artery. 0.05% of participants had isolated protein S deficiency with no concomitant IUGR seen. Patients with protein C and S deficiencies were treated with heparin and progesterone and followed up for pregnancy outcomes. Screening for protein C and S deficiency is mandatory in all cases of recurrent pregnancy loss. Treatment with low molecular weight heparin and progesterone should be initiated to ensure good fetal outcomes and prevent post-partum/postoperative catastrophic venous thromboembolism events.

Association between very advanced maternal age women with gestational diabetes mellitus and the risks of adverse infant outcomes: a cohort study from the NVSS 2014-2019.

BACKGROUND: To evaluate the association between gestational diabetes mellitus (GDM) and infant outcomes in women of very advanced maternal age (vAMA) (≥45 years). METHODS: This cohort study utilized data from the National Vital Statistics System (NVSS) database (2014-2019) in the United States. Preterm birth was the primary outcome, which was subdivided into extremely preterm, very preterm, and moderate or late preterm. The secondary outcomes were neonatal intensive care unit (NICU) admission, low birthweight and small for gestational age. Univariate and multivariate logistic regression analyses were used to explore the association between GDM and infant outcomes among vAMA women. Subgroup analyses were performed based on race and use of infertility treatment. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: A total of 52,544 vAMA pregnant women were included. All analysis made comparisons between women with vAMA and GDM and women with vAMA and no GDM. Women with GDM had a significantly higher risk of preterm birth than those without GDM (OR = 1.26, 95%CI = 1.18-1.36, P < 0.001). Compared with women without GDM, those with GDM had a significantly increased risk of moderate or late preterm birth (OR = 1.27, 95%CI = 1.18-1.37, P < 0.001); no significant association of GDM with extremely preterm birth and very preterm birth was observed. Women with GDM had a significantly greater risk of NICU admission than those without (OR = 1.33, 95%CI = 1.23-1.43, P < 0.001). GDM was associated with a significantly lower risk of low birthweight (OR = 0.91, 95%CI = 0.84-0.98, P = 0.010), and no significant association was found between GDM and small for gestational age (OR = 0.95, 95%CI = 0.87-1.03, P = 0.200) in vAMA women. CONCLUSION: vAMA women with GDM had an increased risk of preterm birth, especially moderate or late preterm birth. NICU admission and low birthweight were also associated with GDM among vAMA women.

Early-onset fetal growth restriction: comparison of two management protocols in a single tertiary center.

OBJECTIVE: Compare the neonatal outcomes of two protocols of diagnosis and surveillance of pregnancies complicated by early-onset FGR in a tertiary hospital. METHODS: This is a retrospective cohort study of pregnant women diagnosed with early-onset FGR between 2017 and 2020. We compared the obstetric and perinatal outcomes between two different management protocols (before and after 2019). RESULTS: Seventy-two cases of early-onset FGR were diagnosed in the forementioned period: 45 (62.5%) were managed according to protocol 1 and 27 (37.5%) according to protocol 2. Mean gestational age at delivery was significantly different between groups: 34.9 ± 3.1 weeks (95% CI 34.0-35.9) in group 1 and 32.3 ± 4.4 weeks (95% CI 30.4-33.9) in group 2. 74.1% (20) of newborns in group 2 were admitted in de NICU, a significant difference when compared with 46.7% of group 1. There were no statistically significant differences in the remaining serious neonatal adverse outcomes. CONCLUSIONS: This is the first study published comparing two different protocols of management of FGR. The implementation of the new protocol seems to have led to a decrease in the number of fetuses labeled as growth restricted and to a decrease in the gestational age of delivery of such fetuses, but without increasing the rate of serious neonatal adverse outcomes. SYNOPSIS: The implementation of the 2016 ISUOG guidelines for the diagnosis of fetal growth restriction seems to have led to a decrease in the number of fetuses labeled as growth restricted and to a decrease in the gestational age of delivery of such fetuses, but without increasing the rate of serious neonatal adverse outcomes.

IL-27 deficiency inhibits proliferation and invasion of trophoblasts via the SFRP2/Wnt/ß-catenin pathway in fetal growth restriction.

Background: Fetal growth restriction (FGR) is characterized by restricted fetal growth and dysregulated placental development. The etiology and pathogenesis still remain elusive. IL-27 shows multiple roles in regulating various biological processes, however, how IL-27 involves in placentation in FGR pregnancy hasn't been demonstrated. Methods: The levels of IL-27 and IL-27RA in FGR and normal placentae were determined by immunohistochemistry, western blot and RT-PCR. HTR-8/SVneo cells and Il27ra-/- murine models have been adopted to evaluate the effects of IL-27 on the bio-functions of trophoblast cells. GO enrichment and GSEA analysis were performed to explore the underlying mechanism. Findings: IL-27 and IL-27RA was lowly expressed in FGR placentae and administration of IL-27 on HTR-8/SVneo could promote its proliferation, migration and invasion. Comparing with wildtypes, Il27ra-/- embryos were smaller and lighter, and the placentae from which were poorly developed. In mechanism, the molecules of canonical Wnt/ß-catenin pathway (CCND1, CMYC, SOX9) were downregulated in Il27ra-/- placentae. In contrast, the expression of SFRP2 (negative regulator of Wnt) was increased. Overexpression of SFRP2 in vitro could impair trophoblast migration and invasion capacity. Interpretation: IL-27/IL-27RA negatively regulates SFRP2 to activate Wnt/ß-catenin, and thus promotes migration and invasion of trophoblasts during pregnancy. However, IL-27 deficiency may contribute to the development of FGR by restricting the Wnt activity.

First-trimester biomarkers and ultrasound biometries in relation to growth discordance in monochorionic diamniotic twins.

Objective: The aim of this study was to investigate the association and predictive value between intertwin discordance in first trimester biometries crown-rump length (CRL) and nuchal translucency (NT), and the first trimester biochemical markers PAPP-A and free ß-hCG in relation to birth weight discordance (BWD) ≥25% in monochorionic diamniotic (MCDA) twin pregnancies.Methods: First trimester screening information and pregnancy outcome data on MCDA twin pregnancies with delivery from July 2008 to July 2017 were retrieved from the Danish Fetal Medicine Database. CRL discordance was divided into: <10% (reference group) and ≥10%. NT discordance was divided into: <20% (reference group) and ≥20%. The twin pregnancies were classified according to BWD into the following groups: <10% (reference group), 10-24.9%, and ≥25% including cases undergoing umbilical cord occlusion due to selective fetal growth restriction (sFGR). The twin pregnancies with the most severe BWD (BWD ≥25%) were subdivided into three groups including cases with only one growth-restricted (<10th centile) infant defined as sFGR, and cases where both twins were <10th centile. Median multiples of the median (MoM) values of PAPP-A and free ß-hCG were compared with the group with BWD <10% using the Wilcoxon two-sample test. The ability of CRL discordance and NT discordance to predict BWD ≥25% was examined by the area under the receiver operator characteristic (ROC) curve.Results: A total of 762 MCDA pregnancies were included. The proportion of pregnancies with CRL discordance ≥10% and NT discordance ≥20% was significantly higher in the group with severe BWD discordance (27.0% vs. 4.7% (p < 0.001) and 40.9% vs. 23.9% (p = 0.001), respectively). When examining the three subgroups of severe BWD, we found a significantly higher percentage of pregnancies with CRL discordance ≥10% in the group where umbilical cord occlusion was performed (52.6% vs. 4.7% in the group with BWD <10% (p < 0.001)) and in the group of BWD ≥25% with sFGR (21.7% vs. 4.7% (p < 0.001)). Additionally, a significantly higher percentage of pregnancies with NT discordance ≥20% was found in the group where umbilical cord occlusion was performed (52.6% vs. 23.9% (p = 0.005)) and in the group with both twins <10th centile (66.7% vs. 23.9% (p = 0.003)). No statistically significant differences were found when comparing levels of PAPP-A and free ß-hCG MoMs with the group with BWD <10%. In ROC curves, CRL discordance yielded an AUC for prediction of BWD ≥25% of 0.70 (95% CI 0.63-0.76), and for NT discordance AUC was 0.59 (95% CI 0.52-0.66)). OR for any BWD ≥ 25% was 6.7 (95% CI 3.8-12.0) for pregnancies with a CRL discordance ≥10% compared to pregnancies with a CRL discordance <10%.Conclusions: This study shows that a discordance in CRL and NT in MCDA twins are both significantly associated with development of BWD. The most important predictor remains CRL discordance ≥10%, thereby suggesting the unequal growth pattern in many cases with BWD is evident already in the first trimester of the pregnancy. No association was found between first trimester biochemical markers and severe BWD.

Predictive index for adverse perinatal outcome in pregnancies complicated by fetal growth restriction.

OBJECTIVES: To develop and validate an index predictive of adverse perinatal outcome (APO) in pregnancies meeting the consensus-based criteria for fetal growth restriction (FGR) endorsed by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). METHODS: This was a retrospective analysis of consecutive singleton non-anomalous gestations meeting the ISUOG-endorsed criteria for FGR at a single tertiary care center from November 2010 to August 2020. The dataset was divided randomly into a development set (two-thirds) and a validation set (one-third). The primary composite APO comprised one or more of: perinatal demise, Grade III-IV intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), seizures, hypoxic ischemic encephalopathy (HIE), necrotizing enterocolitis (NEC), sepsis, bronchopulmonary dysplasia (BPD) and length of stay in the neonatal intensive care unit (NICU) > 7 days. Regression analysis incorporated clinical factors readily available at the time of FGR diagnosis. The sum of ß coefficient-based weights yielded an index score, the performance of which was assessed in the validation set. Score cut-offs were selected to identify 'high-risk' and 'low-risk' ranges for which positive (PPV) and negative (NPV) predictive values and positive (LR+) and negative (LR-) likelihood ratios were calculated. RESULTS: Of the 875 consecutive pregnancies that met the criteria for FGR and were included in the study cohort, 405 (46%) were complicated by one or more components of the composite APO, including 54 (6%) perinatal deaths, 22 (3%) neonates with Grade III-IV IVH and/or PVL, nine (1%) with seizures and/or HIE, 91 (10%) with BPD, 57 (7%) with sepsis, 21 (2%) with NEC, and 361 (41%) who remained in the NICU > 7 days. In addition, 270 (31%) pregnancies were delivered by Cesarean section for non-reassuring fetal status, 43 (5%) were admitted to the NICU for < 7 days, 79 (9%) had 5-min Apgar score < 7, 125/631 (20%) had a cord gas pH ≤ 7.1 and 35/631 (6%) had a base excess ≥ 12 mmol/L. The predictive index we developed included seven factors available at the time of FGR diagnosis: hypertensive disorder of pregnancy (HDP) (+8 points), chronic hypertension without HDP (+4 points), gestational age ≤ 32 weeks (+5 points), absent or reversed end-diastolic flow in the umbilical artery (+8 points), prepregnancy body mass index ≥ 35 kg/m2 (+3 points), isolated abdominal circumference < 3rd percentile (-4 points) and non-Hispanic black race (-2 points). The bias-corrected bootstrapped (1000 replicates) area under the receiver-operating-characteristics curve (AUC) of the predictive index for composite APO in the validation group was 0.88 (95% CI, 0.84-0.92), which was similar to that in the development group (AUC, 0.86 (95% CI, 0.82-0.89); P = 0.34). In the total cohort, 40% of pregnancies had a low-risk index score (≤ 2), associated with a NPV of 85% (95% CI, 81-88%) and a LR- of 0.21 (95% CI, 0.16-0.27), and 23% had a high-risk index score (≥ 10), associated with a PPV of 96% (95% CI, 93-98%) and a LR+ of 27.36 (95% CI, 14.33-52.23). Of the remaining pregnancies that had an intermediate-risk score, 50% were complicated by composite APO. CONCLUSION: An easy-to-use index incorporating seven clinical factors readily available at the time of FGR diagnosis is predictive of APO and may prove useful in counseling and management of pregnancies meeting the ISUOG-endorsed criteria for FGR. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Serum Adipocytokines Profile in Children Born Small and Appropriate for Gestational Age-A Comparative Study.

BACKGROUND: Adipose tissue is not only a storage place for fat, but also an endocrine organ, secreting bioactive molecules which influence body metabolism. Such molecules are known as adipocytokines. In the past years the coincidence between adipocytokines and fetal growth restriction disorders was found. The aim of the study was to estimate serum levels of adiponectin, leptin and resistin in children born small for gestational age, compared to children born at an appropriate size for gestational age. METHODS: The study consisted of 35 children aged seven to nine years, born SGA (small for gestational age) on term and 25 healthy children (14 girls, 11 boys), born with proper birthweight (AGA-appropriate for gestational age)-control group. RESULTS: Adiponectin and leptin levels were significantly higher in the SGA group compared to the AGA group (p = 0.023, p = 0.018 respectively). The resistin values were comparable in both groups of patients. There was a positive correlation between serum leptin concentration and current body weight in SGA group (r = 0.28; p = 0.108). In turn, adiponectin levels in this group of patients negatively correlated with actual body weight (r = -0.51; p = 0.002). The negative correlation between body mass index and plasma adiponectin levels was found only in children born SGA. SGA children had significantly higher values of diastolic blood pressure. There was negative correlation between serum adiponectin level and systolic blood pressure in SGA children. In the SGA group the phenomenon of catch-up growth was observed in 32 children. CONCLUSIONS: Children born SGA have abnormal adipose tissue biomarkers profiles.

Does the Blood-Brain Barrier Integrity Change in Regard to the Onset of Fetal Growth Restriction?

The aim of the study was to determine whether early-onset and late-onset fetal growth restriction (FGR) differentially affects the blood-brain barrier integrity. Furthermore, the purpose of the study was to investigate the relationship between the blood-brain barrier breakdown and neurological disorders in FGR newborns. To evaluate the serum tight junction (TJ) proteins and the placental TJ proteins expression, an ELISA method was used. A significant difference in serum OCLN concentrations was noticed in pregnancies complicated by the early-onset FGR, in relation to the intraventricular hemorrhage (IVH) occurrence in newborns. No significant differences in concentrations of the NR1 subunit of the N-methyl-d-aspartate receptor (NR1), nucleoside diphosphate kinase A (NME1), S100 calcium-binding protein B (S100B), occludin (OCLN), claudin-5 (CLN5), zonula occludens-1 (zo-1), the CLN5/zo-1 ratio, and the placental expression of OCLN, CLN5, claudin-4 (CLN4), zo-1 were noticed between groups. The early-onset FGR was associated with a higher release of NME1 into the maternal circulation in relation to the brain-sparing effect and premature delivery. Additionally, in late-onset FGR, the higher release of the S100B into the maternal serum in regard to fetal distress was observed. Furthermore, there was a higher release of zo-1 into the maternal circulation in relation to newborns' moderate acidosis in late-onset FGR. Blood-brain barrier disintegration is not dependent on pregnancy advancement at the time of FGR diagnosis. NME1 may serve as a biomarker useful in the prediction of fetal circulatory centralization and extremely low birth weight in pregnancies complicated by the early-onset FGR. Moreover, the serum zo-1 concentration may have prognostic value for moderate neonatal acidosis in late-onset FGR pregnancies.

Heterogenous Differences in Cellular Senescent Phenotypes in Pre-Eclampsia and IUGR following Quantitative Assessment of Multiple Biomarkers of Senescence.

Premature ageing of the placenta in pregnancy outcomes is associated with the persistent presence of oxidative stress and placental insufficiency reducing its functional capacity. In this study, we investigated cellular senescence phenotypes of pre-eclampsia and IUGR pregnancies by simultaneously measuring several biomarkers of senescence. Maternal plasma and placental samples were collected at term gestation from nulliparous women undergoing pre-labour elective caesarean section with pre-eclampsia without intrauterine growth restriction (PE; n = 5), pre-eclampsia associated with intrauterine growth restriction (n = 8), intrauterine growth restriction (IUGR < 10th centile; n = 6), and age-matched controls (n = 20). Placental absolute telomere length and senescence gene analysis was performed by RTqPCR. The expression of cyclin-dependent kinase inhibitors (p21 and p16) was determined by Western blot. Senescence-associated secretory phenotypes (SASPs) were evaluated in maternal plasma by multiplex ELISA assay. Placental expression of senescence-associated genes showed significant increases in CHEK1, PCNA, PTEN, CDKN2A, and CCNB-1 (p < 0.05) in pre-eclampsia, while TBX-2, PCNA, ATM, and CCNB-1 expression were evident (p < 0.05) and were significantly decreased in IUGR compared with controls. Placental p16 protein expression was significantly decreased in pre-eclampsia only compared with controls (p = 0.028). IL-6 was significantly increased in pre-eclampsia (0.54 pg/mL ± 0.271 vs. 0.3 pg/mL ± 0.102; p = 0.017) while IFN-γ was significantly increased in IUGR (4.6 pg/mL ± 2.2 vs. 2.17 pg/mL ± 0.8; p = 0.002) compared with controls. These results provide evidence of premature senescence in IUGR pregnancies, and while cell cycle checkpoint regulators are activated in pre-eclampsia, the cellular phenotype is one of cell repair and subsequent proliferation rather than progression to senescence. The heterogeneity of these cellular phenotypes highlights the complexity of characterising cellular senescence and may equally be indicative of the differing pathophysiological insults unique to each obstetric complication.

Modification effects of ambient temperature on associations of ambient ozone exposure before and during pregnancy with adverse birth outcomes: A multicity study in China.

BACKGROUND: Epidemiological studies suggest that both ambient ozone (O3) and temperature were associated with increased risks of adverse birth outcomes. However, very few studies explored their interaction effects, especially for small for gestational age (SGA) and large for gestational age (LGA). OBJECTIVES: To estimate the modification effects of ambient temperature on associations of ambient O3 exposure before and during pregnancy with preterm birth (PTB), low birth weight (LBW), SGA and LGA based on multicity birth cohorts. METHODS: A total of 56,905 singleton pregnant women from three birth cohorts conducted in Tianjin, Beijing and Maoming, China, were included in the study. Maximum daily 8-h average O3 concentrations of each pregnant woman from the preconception period to delivery for every day were estimated by matching their home addresses with the Tracking Air Pollution in China (TAP) datasets. We first applied the Cox proportional-hazards regression model to evaluate the city-specific effects of O3 exposure before and during pregnancy on adverse birth outcomes at different temperature levels with adjustment for potential confounders, and then a meta-analysis across three birth cohorts was conducted to calculate the pooled associations. RESULTS: In pooled analysis, significant modification effects of ambient temperature on associations of ambient O3 with PTB, LBW and LGA were observed (Pinteraction < 0.05). For a 10 µg/m3 increase in ambient O3 exposure at high temperature level (> 75th percentile), the risk of LBW increased by 28 % (HR: 1.28, 95% CI: 1.13-1.46) during the second trimester and the risk of LGA increased by 116% (HR: 2.16, 95%CI: 1.16-4.00) during the entire pregnancy, while the null or weaker association was observed at corresponding low (≤ 25th percentile) and medium (> 25th and ≤ 75th percentile) temperature levels. CONCLUSION: This multicity study added new evidence that ambient high temperature may enhance the potential effects of ambient O3 on adverse birth outcomes.

Abnormal Maternal Body Mass Index and Customized Fetal Weight Charts: Improving the Identification of Small for Gestational Age Fetuses and Newborns.

BACKGROUND: Obesity and thinness are serious diseases, but cases with abnormal maternal weight have not been excluded from the calculations in the construction of customized fetal growth curves (CCs). METHOD: To determine if the new CCs, built excluding mothers with an abnormal weight, are better than standard CCs at identifying SGA. A total of 16,122 neonates were identified as SGA, LGA, or AGA, using the two models. Logistic regression and analysis of covariance were used to calculate the OR and CI for adverse outcomes by group. Gestational age was considered as a covariable. RESULTS: The SGA rates by the new CCs and by the standard CCs were 11.8% and 9.7%, respectively. The SGA rate only by the new CCs was 18% and the SGA rate only by the standard CCs was 0.01%. Compared to AGA by both models, SGA by the new CCs had increased rates of cesarean section, (OR 1.53 (95% CI 1.19, 1.96)), prematurity (OR 2.84 (95% CI 2.09, 3.85)), NICU admission (OR 5.41 (95% CI 3.47, 8.43), and adverse outcomes (OR 1.76 (95% CI 1.06, 2.60). The strength of these associations decreased with gestational age. CONCLUSION: The use of the new CCs allowed for a more accurate identification of SGA at risk of adverse perinatal outcomes as compared to the standard CCs.

Influence of different methods for calculating gestational age at birth on prematurity and small for gestational age proportions: a systematic review with meta-analysis.

BACKGROUND: Recognizing premature newborns and small-for-gestational-age (SGA) is essential for providing care and supporting public policies. This systematic review aims to identify the influence of the last menstrual period (LMP) compared to ultrasonography (USG) before 24 weeks of gestation references on prematurity and SGA proportions at birth. METHODS: Systematic review with meta-analysis followed the recommendations of the PRISMA Statement. PubMed, BVS, LILACS, Scopus-Elsevier, Embase-Elsevier, and Web-of-Science were searched (10-30-2022). The research question was: (P) newborns, (E) USG for estimating GA, (C) LMP for estimating GA, and (O) prematurity and SGA rates for both methods. Independent reviewers screened the articles and extracted the absolute number of preterm and SGA infants, reference standards, design, countries, and bias. Prematurity was birth before 37 weeks of gestation, and SGA was the birth weight below the p10 on the growth curve. The quality of the studies was assessed using the New-Castle-Ottawa Scale. The difference between proportions estimated the size effect in a meta-analysis of prevalence. RESULTS: Among the 642 articles, 20 were included for data extraction and synthesis. The prematurity proportions ranged from 1.8 to 33.6% by USG and varied from 3.4 to 16.5% by the LMP. The pooled risk difference of prematurity proportions revealed an overestimation of the preterm birth of 2% in favor of LMP, with low certainty: 0.02 (95%CI: 0.01 to 0.03); I2 97%). Subgroup analysis of USG biometry (eight articles) showed homogeneity for a null risk difference between prematurity proportions when crown-rump length was the reference: 0.00 (95%CI: -0.001 to 0.000; I2: 0%); for biparietal diameter, risk difference was 0.00 (95%CI: -0.001 to 0.000; I2: 41%). Only one report showed the SGA proportions of 32% by the USG and 38% by the LMP. CONCLUSIONS: LMP-based GA, compared to a USG reference, has little or no effect on prematurity proportions considering the high heterogeneity among studies. Few data (one study) remained unclear the influence of such references on SGA proportions. Results reinforced the importance of qualified GA to mitigate the impact on perinatal statistics. TRIAL REGISTRATION: Registration number PROSPERO: CRD42020184646.

Evaluation of Doppler indices (MCA & UA) and fetal outcomes: a retrospective case-control study in women with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is associated with an increased risk of adverse outcomes. The fetal middle cerebral artery (MCA) and umbilical artery (UA) blood flow detected by ultrasound are recommended to evaluate the oxygenation of the fetus. It is necessary to analyze the relationship between MCA & UA doppler indices or cerebroplacental ratio (CPR) and fetal outcomes and describe MCA and UA blood flow values across gestation. METHODS: Hospital-based retrospective case-control study during 2016 to 2020. 800 singleton pregnant women: 400 normotensive control, 219 gestational hypertension (GH), and 181 preeclampsia (PE)/eclampsia (EC). An analysis of the outcomes of mothers and neonates was performed. The fetal MCA and UA blood flow values across gestation were established, and MCA-resistance index (RI) and CPR were used to predict fetal distress and small for gestational age (SGA). RESULTS: In the normotensive control, GH and PE/EC groups, the mean gestational age (GA) was 38.9 ± 1.2 weeks, 39.0 ± 1.0 weeks, and 38.6 ± 1.3 weeks respectively, and the mean birth weight (BW) was 3.195 ± 0.387 kilograms, 3.198 ± 0.428 kilograms, and 2.987 ± 0.544 kilograms respectively. There were differences in GA, BW, fetal distress, SGA and intraventricular hemorrhage I-II between the hypertension group and normotensive control group (p < 0.05). The MCA-RI (sensitivity: 70.1%, specificity: 64.3%) and MCA-RI (sensitivity: 52.4%, specificity: 84.6%) were the best indices to predict fetal distress and SGA, respectively during GA of 35-40 weeks. CONCLUSIONS: Fetal MCA blood flow values and CPR are of great benefit for obstetricians to evaluate the status of fetus evidentially in singleton pregnancy.

Analysis of the anemia characteristics in early pregnancy and outcomes of pregnant women with hemoglobin H disease.

OBJECTIVE: This study aimed to analyze the anemia characteristics in early pregnancy of pregnant women with hemoglobin H (Hb H) disease and their pregnancy outcomes, and to provide reference to the pregnancy management and treatment of these women. PATIENTS AND METHODS: Twenty-eight cases of pregnant women who had been diagnosed with Hb H disease in the Second Affiliated Hospital of Guangxi Medical University from August 2018 to March 2022 were retrospectively analyzed. Moreover, 28 cases of normal pregnant women in the same period were randomly enrolled as a control group for comparison. The means and percentages of the anemia characteristics in early pregnancy and the pregnancy outcomes were calculated and the analysis of variance, Chi-square test, and Fisher's exact test were applied for comparison. RESULTS: A total of 13 cases of missing type (46.43%) and 15 cases of non-missing type (53.57%) were observed in the 28 cases of pregnant women with Hb H disease. The genotypes were as follows: 8 cases of -α3.7/--SEA (28.57%), 4 cases of -α4.2/--SEA (14.29%), 1 case of -α4.2/--THAI (3.57%), 9 cases of αCSα/--SEA (32.14%), 5 cases of αWSα/--SEA (17.86%), and 1 case of αQSα/--SEA (3.57%). Twenty-seven patients with Hb H disease (96.43%) were anemic, including 5 cases of mild anemia (17.86%), 18 cases of moderate anemia (64.28%), 4 cases of severe anemia (14.29%), and 1 case of non-anemia (3.57%). Compared with the control group, the Hb H group had significantly higher red blood cell count and significantly lower Hb, mean corpuscular volume, and mean corpuscular hemoglobin, and the differences were statistically significant (p < 0.05). The Hb H group had higher incidence rates of blood transfusion during pregnancy (BTDP), oligohydramnios fetal growth restrictions (FGR), and fetal distress than the control group. The weights of neonates were lower in the Hb H group than in the control group. Statistically significant differences were found between these two groups (p < 0.05). CONCLUSIONS: The genotype missing type of pregnant women with Hb H disease was mainly -α3.7/--SEA and the non-missing type was mainly αCSα/--SEA. Hb H disease can easily cause various degrees of anemia (mainly moderate anemia in this study). Moreover, it can increase the incidence rate of pregnancy complications such as BTDP, oligohydramnios, FGR, and fetal distress, which will reduce the weight of neonates and seriously affect maternal and infant safety. Therefore, maternal anemia and fetal growth and development should be monitored during pregnancy and delivery, and transfusion therapy should be used to improve adverse pregnancy outcomes caused by anemia when necessary.

Antenatal corticosteroid administration-to-birth interval and neonatal outcomes in very preterm infants: A secondary analysis based on a prospective cohort study.

INTRODUCTION: Despite the prevalent use of antenatal corticosteroids (ACS) to prevent preterm infants' adverse neonatal complications, there is currently no consensus on administration-to-birth intervals of ACS. International guidelines broadly agree that the administration of antenatal corticosteroids should be within 7 days prior to preterm birth. However, there is little evidence to support narrower optimal ACS administration-to-birth interval time. This study was undertaken to investigate the association between the administration-to-birth interval of ACS which is bounded by 48 hours and neonatal outcomes in very preterm infants. MATERIALS AND METHODS: This is a single-center prospective observational study. Data were collected prospectively from eligible infants from January 2008 to April 2014 at the Santa Clara Valley Medical Center, neonatal outcomes were compared between two groups based on the interval of antenatal corticosteroid administration-to-birth: the interval of <48h, and the interval of >48h. It was noted that the entire study was completed by Dongli Song et al., and uploaded the data to the DATADRYAD website. The author only used this data for secondary analysis. RESULTS: After adjusting potential confounders (gestational age, sex, birth weight, duration of cord clamping and delivery mode), the interval of >48h group compared to the interval of <48h group had significant reductions in mortality (OR: 0.17; 95% CI: 0.05-0.59), any retinopathy of prematurity (OR: 0.36; 95% CI: 0.16-0.82), severe retinopathy of prematurity (OR: 0.07; 95% CI: 0.01-0.45), any intubation (OR: 0.39; 95% CI: 0.20-0.75) and higher 1 min Apgar (ß: 0.56; 95% CI: 0.10-1.02). CONCLUSION: This study shows that in very preterm infants, compared with the interval of ACS<48h, the interval of ACS>48 hours has a significant health promotion effect.

Neonatal hematological parameters: the translational aspect of developmental hematopoiesis.

Hematopoiesis is a process constantly evolving from fetal life through adulthood. Neonates present with qualitative and quantitative differences in hematological parameters compared to older children and adults, reflecting developmental changes in hematopoiesis correlated with gestational age. Such differences are more intense for preterm and small-for-gestational-age neonates or neonates with intrauterine growth restriction. This review article is aimed at describing the hematologic differences among neonatal subgroups and the major underlying pathogenic mechanisms. Issues that should be taken into account when interpreting neonatal hematological parameters are also highlighted.

Regulators involved in trophoblast syncytialization in the placenta of intrauterine growth restriction.

Placental dysfunction refers to the insufficiency of placental perfusion and chronic hypoxia during early pregnancy, which impairs placental function and causes inadequate supply of oxygen and nutrients to the fetus, affecting fetal development and health. Fetal intrauterine growth restriction, one of the most common outcomes of pregnancy-induced hypertensions, can be caused by placental dysfunction, resulting from deficient trophoblast syncytialization, inadequate trophoblast invasion and impaired vascular remodeling. During placental development, cytotrophoblasts fuse to form a multinucleated syncytia barrier, which supplies oxygen and nutrients to meet the metabolic demands for fetal growth. A reduction in the cell fusion index and the number of nuclei in the syncytiotrophoblast are found in the placentas of pregnancies complicated by IUGR, suggesting that the occurrence of IUGR may be related to inadequate trophoblast syncytialization. During the multiple processes of trophoblasts syncytialization, specific proteins and several signaling pathways are involved in coordinating these events and regulating placental function. In addition, epigenetic modifications, cell metabolism, senescence, and autophagy are also involved. Study findings have indicated several abnormally expressed syncytialization-related proteins and signaling pathways in the placentas of pregnancies complicated by IUGR, suggesting that these elements may play a crucial role in the occurrence of IUGR. In this review, we discuss the regulators of trophoblast syncytialization and their abnormal expression in the placentas of pregnancies complicated by IUGR.