The Contribution of Hypertensive Disorders of Pregnancy to Neonatal Unit Admissions and Iatrogenic Preterm Delivery at < 34+0 Weeks' Gestation in the UK: A Population-Based Study Using the National Neonatal Research Database.

OBJECTIVES: The objectives of this study were to (i) quantify the contribution of maternal hypertensive disorders of pregnancy (HDP) to iatrogenic preterm birth (PTB) and neonatal unit (NNU) admissions < 34+0 weeks and (ii) describe short-term population-level outcomes for HDP infants, exploring ethnic disparities and comparing outcomes by HDP exposure. DESIGN: Retrospective population-based study using the National Neonatal Research Database. SETTING: England and Wales. POPULATION: Infants born < 34+0 weeks and admitted to NNU 2012-2020. METHODS: Descriptive statistics, linear and logistic regression models to compare outcomes between groups. MAIN OUTCOME MEASURES: Survival to discharge with/without comorbidity. RESULTS: 122 228 infants met inclusion criteria. Where collected, 49 839/114 164 (43.7%, 95% CI 43.4%-43.9%) of infants had an iatrogenic PTB. HDP was recorded in 16 510/122 228 (13.5%) of all infants and 13 560/49 839 (27.2%) of iatrogenic PTBs. HDP and/or foetal growth restriction (FGR) were recorded in 24 124/49 839 (48.4%) of iatrogenic PTBs. Singleton HDP infants < 10th BWC had ≥ 90% survival to discharge from 28 weeks' gestation, versus from 26 weeks' gestation for those born ≥ 10th BWC. In extreme preterm HDP infants (< 27 weeks), 27.3% of infants < 10th BWC died compared to 15.2% of those ≥ 10th BWC. Survival without comorbidity was ≥ 90% from 32 weeks' gestation in HDP infants across BWC. CONCLUSIONS: These contemporaneous population-level data show that almost one in two PTB < 34+0 weeks' gestation are iatrogenic, with HDP and/or FGR being the major contributors to iatrogenic prematurity. This has substantial implications for strategies to reduce preterm birth in the UK and internationally. The data further inform antenatal and at-birth counselling of HDP-exposed infants.

Expression and significance of CEMIP and CYP11B2 in serum in women with foetal growth restriction.

BACKGROUND: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR. METHODS: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed. RESULTS: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P < 0.001). CEMIP (95%CI: 0.802-0.921, P < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P < 0.001) were independent predictors of FGR, and CEMIP (r = -0.578, P = 0.001) and CYP11B2 (r = -0.602, P < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR. CONCLUSION: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.

Foetal growth restriction is the inability of the foetus to reach its growth potential in the uterus due to various factors. This study aimed to investigate the expression and significance of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction. In our study, we found that the expression of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction were decreased. Cell migration-including protein and aldosterone synthase expression was negatively correlated with soluble fms like tyrosine kinase-1/placental growth factor ratio. In addition, the study also found that cell migration-including protein and aldosterone synthase expression in serum had good diagnostic value for foetal growth restriction.

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.

Impact on neonatal morbidity of moderate to severe early foetal growth restriction defined by doppler criteria: multicentre study.

INTRODUCTION: In recent years, there has been a change in the conceptualization of foetal growth restriction (FGR), which has gone from being defined solely based on weight criteria to being defined and staged based on Doppler criteria. The aim of our study was to evaluate neonatal risk in a cohort of neonates with moderate to severe early-onset FGR defined by Doppler criteria. POPULATION AND METHODS: We conducted a multicentre prospective cohort study in a cohort of neonates with early-onset foetal growth restriction and abnormal Doppler findings and a control cohort without Doppler abnormalities matched for sex and gestational age. RESULTS: A total of 105 patients (50 cases, 55 controls) were included. We found a higher frequency of respiratory morbidity in the FGR group, with an increased need of surfactant (30% vs. 27.3%; OR, 5.3 [95% CI, 1.1-26.7]), an increased need for supplemental oxygen (66% vs. 49.1%; OR, 5.6 [95% CI, 1.5-20.5]), and a decreased survival without bronchopulmonary dysplasia (70 vs. 87.3%; OR, 0.16 [95% CI, 0.03-0.99]). Patients with FGR required a longer length of stay and more days of parenteral nutrition and had a higher incidence of haematological abnormalities such as neutropenia and thrombopenia. The lactate level at birth was higher in the severe FGR subgroup (6.12 vs. 2.4 mg/dL; P = .02). CONCLUSION: The diagnosis of early-onset moderate to severe FGR defined by Doppler criteria carries a greater risk of respiratory, nutritional and haematological morbidity, independently of weight and gestational age. These patients, therefore, should be considered at increased risk compared to constitutionally small for gestational age preterm infants or preterm infants without FGR.

Treatment of parathormone-dependent hypercalcaemia in the third-trimester of pregnancy.

Not required for Clinical Vignette.

Perinatal features of children with Silver-Russell syndrome due to 11p15 loss of methylation.

Background: A diagnosis of Silver-Russell syndrome (SRS), a rare imprinting disorder responsible for foetal growth restriction, is considered for patients presenting at least four criteria of the Netchine-Harbison clinical scoring system (NH-CSS). Certain items of the NH-CSS are not assessable until the age of 2 years. The objective was to determine perinatal characteristics of children with SRS to allow an early diagnosis. Methods: We retrospectively compared the perinatal characteristics of children with SRS (n = 17) with those of newborns small for gestational age (SGA) due to placental insufficiency (PI) (n = 21). Results: Children with SRS showed earlier and more severely altered foetal biometry than SGA newborns due to PI. Twenty-three percent of patients with SRS showed uterine artery Doppler anomalies. SRS children were significantly smaller at birth (birth length <-3 SDS in 77% of cases in the SRS group vs. 15% in the PI group, p = 0.0001). Conclusion: The diagnosis of SRS must be evoked in the neonatal period for SGA newborns with a growth delay present from the second trimester of pregnancy, a birth length <-3 SDS and a relative macrocephaly. Doppler anomalies, classically used to orient the cause of SGA towards PI, did not rule out the diagnosis of SRS.

Reduced T2*-weighted placental MRI predicts foetal growth restriction in women with chronic rheumatic disease-a Danish explorative study.

OBJECTIVES: Women with chronic rheumatic disease (CRD) are at greater risk of foetal growth restriction than their healthy peers. T2*-weighted magnetic resonance imaging of placenta (T2*P-MRI) is superior to conventional ultrasonography in predicting birth weight and works as a proxy metabolic mirror of the placental function. We aimed to compare T2*P-MRI in pregnant women with CRD and healthy controls. In addition, we aimed to investigate the correlation between T2*P-MRI and birth weight. METHODS: Using a General Electric (GE) 1.5 Tesla, we consecutively performed T2*-weighted placental MRI in 10 women with CRD and 18 healthy controls at gestational week (GW)24 and GW32. We prospectively collected clinical parameters during pregnancy including birth outcome and placental weight. RESULTS: Women with CRD had significantly lower T2*P-MRI values at GW24 than healthy controls (median T2*(IQR) 92.1 ms (81.6; 122.4) versus 118.6 ms (105.1; 129.1), p = 0.03). T2*P-MRI values at GW24 showed a significant correlation with birth weight, as the T2*P-MRI value was reduced in all four pregnancies complicated by SGA at birth. Three out of four pregnancies complicated by SGA at birth remained undetected by routine antenatal ultrasound. CONCLUSION: This study demonstrates reduced T2*P-MRI values and a high proportion of SGA at birth in CRD pregnancies compared to controls, suggesting an increased risk of placental dysfunction in CRD pregnancies. T2*P-MRI may have the potential to focus clinical vigilance by identifying pregnancies at risk of SGA as early as GW24. Key Points • Placenta-related causes of foetal growth restriction in women with rheumatic disease remain to be investigated. • T2*P-MRI values at gestational week 24 predicted foetuses small for gestational age at birth. • T2*P-MRI may indicate pregnant women with chronic rheumatic disease (CRD) in need of treatment optimization.

Mitochondrial quality control alterations and placenta-related disorders.

Mitochondria are ubiquitous in eukaryotic cells. Normal maintenance of function is the premise and basis for various physiological activities. Mitochondrial dysfunction is commonly observed in a wide range of pathological conditions, such as neurodegenerative, metabolic, cardiovascular, and various diseases related to foetal growth and development. The placenta is a highly energy-dependent organ that acts as an intermediary between the mother and foetus and functions to maintain foetal growth and development. Recent studies have demonstrated that mitochondrial dysfunction is associated with placental disorders. Defects in mitochondrial quality control mechanisms may lead to preeclampsia and foetal growth restriction. In this review, we address the quality control mechanisms of mitochondria and the relevant pathologies of mitochondrial dysfunction in placenta-related diseases, such as preeclampsia and foetal growth restriction. This review also investigates the relation between mitochondrial dysfunction and placental disorders.

Association between small-for-gestational age and poor school performance in 2 500 000 children born 1973-2002.

AIM: To examine the association between infant weight for gestational age and school performance when leaving school at 16 years of age. METHODS: Out of 2 525 571 infants born near- or at term, between 1 January 1973 and 31 December 2002, identified from the Swedish Medical Birth Register, 65 912 (2.6%) were born small-for-gestational age (SGA). Outcomes studied were the risk for the need for education in special school, and the final average grades. Modified Poisson regression analyses and weighted linear regression analyses were performed. RESULTS: An association between SGA and the need for a special school was found, irrespective of restrictions or adjustments (RR between 2.47 and 2.25). SGA was associated with final grades below the 10th and 25th percentile (RR 1.49 and 1.18, respectively). A linear relationship between maternal height and the RR for education in special school (p = 0.005), suggested that SGA is a stronger risk factor among children of tall than of shorter women. CONCLUSION: SGA increased the risk for poor school performance, and for the need for a special school. We found an association between maternal height and school performance in relation to birthweight, suggesting that maternal height should be considered when estimating the impact of SGA on later outcomes.

The head circumference to chest circumference ratio provided an easy way to detect foetal growth restriction in term infants.

AIM: The head circumference to chest circumference (HC/CC) ratio has been used to identify low birth weight infants in developed countries. This study was conducted to examine whether the ratio could distinguish asymmetrical foetal growth restriction (FGR). METHODS: This retrospective observational study was conducted with 1955 infants (50.5% male) born at term between 2016 and 2020 at Tokyo Metropolitan Toshima Hospital, Japan. RESULTS: We found that 120 (6.1%) had FGR. Their mean birth weight was 3052.1 ± 367.3 g, and their mean gestational age was 39.1 ± 1.1 weeks. Logistic regression analysis showed that the association between the HC/CC ratio and FGR had a regression coefficient of -20.6 (p < 0.000). The linear regression analysis showed that the association between the HC/CC ratio and the birth weight z-score had a regression coefficient of -8.59 (p < 0.000). The coefficient of correlation was -0.33 (p < 0.001). The receiver operating characteristic curve for detecting FGR showed that the area under the curve was 0.75 and the cut-off value was 0.93, with sensitivity of 75.8% and specificity of 60.8%. CONCLUSION: Our study established the associations between HC/CC ratio and FGR and birth weight z-scores and confirmed that the ratio provided an easy way to detect FGR in term-born infants.

Angiogenic growth factors, oxidative stress and haematobiochemical measures as predictors of preeclampsia with and without foetal growth restriction: A case-control study in a Ghanaian population.

INTRODUCTION: This study compares the angiogenic growth mediators (AGMs), oxidative stress (OS) and haematobiochemical profile as well as foeto-maternal outcomes of preeclampsia (PE) with and without foetal growth restriction (FGR) and the discriminative potential of these markers for identifying these conditions. METHODS: This hospital-based case-control study recruited a total of 209 women including 109 PE women without FGR and 48 PE women with FGR as cases whereas 52 normotensive pregnant women were recruited as controls. OS and AGMs and haematobiochemical markers were measured for all participants. RESULTS: The rates of foetal complications including intrauterine foetal death and foetal distress were more common in PE with FGR than PE without FGR (p < 0.05) but maternal complications were comparable across these groups (p > 0.05). Of the haematobiochemical markers, placental growth factors (PIGF), PIGF/8-Isoprostane, sFlt-1/PIGF (AUC = 0.87, p < 0.001), soluble FMS-tyrosine kinase receptor-1 (sFlt-1) (AUC = 0.85, p < 0.001), total antioxidant capacity, 8-isoprostane (AUC = 0.83, p < 0.001) and lactate dehydrogenase (AUC = 0.70, p < 0.001) were more associated and showed at least an acceptable discrimination for PE with FGR against PE only. DISCUSSION: The occurrence of FGR in PE patients does not necessarily indicate a severe maternal presentation of the condition but a tendency for adverse foetal outcomes. Cumulative assessment of OS and AGMs may provide diagnostic usefulness for distinguishing PE with and without FGR.

Human placental vascular and perivascular cell heterogeneity differs between first trimester and term, and in pregnancies affected by foetal growth restriction.

Growth-restricted placentae have a reduced vascular network, impairing exchange of nutrients and oxygen. However, little is known about the differentiation events and cell types that underpin normal/abnormal placental vascular formation and function. Here, we used 23-colour flow cytometry to characterize placental vascular/perivascular populations between first trimester and term, and in foetal growth restriction (FGR). First-trimester endothelial cells had an immature phenotype (CD144+/lowCD36-CD146low), while term endothelial cells expressed mature endothelial markers (CD36+CD146+). At term, a distinct population of CD31low endothelial cells co-expressed mesenchymal markers (CD90, CD26), indicating a capacity for endothelial to mesenchymal transition (EndMT). In FGR, compared with normal pregnancies, endothelial cells constituted 3-fold fewer villous core cells (P < 0.05), contributing to an increased perivascular: endothelial cell ratio (2.6-fold, P < 0.05). This suggests that abnormal EndMT may play a role in FGR. First-trimester endothelial cells underwent EndMT in culture, losing endothelial (CD31, CD34, CD144) and gaining mesenchymal (CD90, CD26) marker expression. Together this highlights how differences in villous core cell heterogeneity and phenotype may contribute to FGR pathophysiology across gestation.

Successful Pregnancy Outcome in an Operated Case of Budd-Chiari Syndrome Having Fetal Growth Restriction: A Twisted Tale of Gravid.

Budd-Chiari Syndrome (BCS) primarily affects women in the reproductive age group, with an ever-increasing incidence in the general population. Due to its rarity, it is not known precisely how a pregnancy progresses in a woman with BCS and what can happen to the baby. A rare condition known as Budd-Chiari syndrome causes the hepatic veins in the liver to constrict and become blocked. The challenges in pregnancy, such as decreasing hepatic function, a rise in thrombotic and bleeding events, or ascites, have historically made pregnancy inappropriate in these people. Here, we present a case of an unbooked 24-year-old female, a known case of treated BCS with 36 weeks and three days gestation period. She was referred from a peripheral hospital to our hospital's emergency department because of having fetal growth restriction. By presenting this rare case, we expect more extensive studies will be conducted on the effect of pregnancy on BCS and the effect of BCS on pregnancy which will help obstetricians to turn this rare possibility of conception into a fair possibility.

Neurodevelopmental outcomes of very preterm infants born following early foetal growth restriction with absent end-diastolic umbilical flow.

This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes and on preterm infants' clinical and neurodevelopmental outcomes up to 2 years corrected age. This is a retrospective, cohort study led at a level IV Obstetric and Neonatal Unit in Bologna, Italy. Pregnant women were eligible if having singleton pregnancies, with no major foetal anomaly detected, and diagnosed with early FGR + AEDF (defined as FGR + AEDF detected before 32 weeks gestation). Early FGR + AEDF was further classified according to time of onset and specific features into very early and persistent (VEP, FGR + AEDF first detected at 20-24 weeks gestation and persistent at the following scans), very early but transient (VET, FGR + AEDF detected at 20-24 weeks gestation and progressively improving at the following scans) and later (LA, FGR + AEDF detected between 25 and 32 weeks gestation). Pregnancy and neonatal outcomes and infant follow-up data were collected and compared among groups. Neurodevelopment was assessed using the revised Griffiths Mental Developmental Scales (GMDS-R) 0-2 years. A regression analysis was performed to identify early predictors of preterm infants' neurodevelopmental impairment. Fifty-two pregnant women with an antenatal diagnosis of early FGR + AEDF were included in the study (16 VEP, 14 VET, 22 LA). Four intrauterine foetal deaths occurred, all in the VEP group (p = 0.010). Compared to LA infants, VEP infants were born with lower gestational age and lower birth weight, had lower arterial cord blood pH and were at higher risk for intraventricular haemorrhage and periventricular leukomalacia (p < 0.05 for all comparisons). At 12 months, VEP infants had worse GMDS-R scores, both in the general quotient (mean [SD] 91.8 [12.4] vs 104.6 [8.7] in LA) and in the performance domain (mean [SD] 93.3 [15.4] vs 108.8 [8.8] in LA). This latter difference persisted at 24 months (mean [SD] 68.3 [17.0] vs 92.9 [17.7] in LA). In multivariate analysis, at 12 months corrected age, PVL was found to be an independent predictor of impaired general quotient, while the features and timing of antenatal Doppler alterations predicted worse scores in the performance domain.   Conclusion: Timing of onset and features of early FGR + AEDF might impact differently on neonatal clinical and neurodevelopmental outcomes. Shared awareness of the importance of FGR + AEDF features between obstetricians and neonatologists may offer valuable tools for antenatal counselling and for tailoring pregnancy management and neonatal follow-up in light of specific antenatal and neonatal risk factors. What is Known: • Foetal growth restriction (FGR), together with antenatal umbilical Doppler abnormalities, is known to affect maternal and neonatal outcomes. • Infants born preterm and growth-restricted face the highest risk for neurodevelopmental impairment, especially when FGR occurs early during pregnancy (early FGR, before 32 weeks gestation). What is New: • The timing of onset and features of FGR and antenatal umbilical Doppler abnormalities impact differently on maternal and neonatal outcomes; when FGR and Doppler abnormalities occur very early, at the limit of neonatal viability, and persist until delivery, infants face the highest risk for neurodevelopmental impairment. • Shared knowledge between obstetricians and neonatologists about timing of onset and features of FGR would provide a valuable tool for informed antenatal counselling in high-risk pregnancies.

Risk Factors Associated With Intrauterine Growth Restriction: A Case-Control Study.

Background Intrauterine growth restriction (IUGR) is a disorder in which the fetus fails to reach its genetic development potential and is considered to be present when the weight at birth is less than the 10th percentile; as a result, it is at risk of increased postnatal morbidity and mortality. Every year, approximately 24% of newborns worldwide are determined to have IUGR. The objective of the present study was to identify various sociodemographic, medical, and obstetric risk factors associated with IUGR. Methodology A case-control study was conducted from January 2020 to December 2022. Fifty-four cases and 54 controls were included in the study. Postnatal women with neonates having birth weight below the 10th percentile for gestational age (GA) were recruited as cases in the study. Control cases were postnatal women with neonatal birth weight appropriate for (GA). Detailed history with respect to socio-demographic, medical, and obstetric parameters was noted and compared. Results Among the sociodemographic factors, only socioeconomic status showed significant statistical differences with the age group of 21 to 25 years showing maximum (51.9%) IUGR cases. Among the maternal risk factors, anemia (29.6%) and hypertensive disorders of pregnancy (22.2%) were marked as significant risk factors for IUGR. There was no significant difference in the distribution of past medical and obstetric histories between the two research groups. Conclusion Due to the poor living conditions, low literacy rates, and general lack of knowledge, low socioeconomic level increases the risk of IUGR. This leads to nutritional deficiencies and insufficient growth environment which results in anemia and hypertensive disorders of pregnancy which are potent risk factors for IUGR. IUGR may be caused by maternal risk factors as well as past medical and obstetric conditions. However, for the risk factor of IUGR, the birth weight at the time of delivery could be taken into consideration as well.

Matrix metalloproteinase-3 in preeclamptic and normotensive pregnancies complicated by foetal growth restriction.

The aim of the present study was to assess the interrelationships between the level of matrix metalloproteinase-3 in the blood serum of pregnant women and the occurrence of pregnancy complications in the form of foetal growth restriction, idiopathic or in the course of preeclampsia. Methods: A total of 245 patients were included in the study. 65 of them are normotensive patients with idiopathic foetal growth restriction (FGR group). 115 women were diagnosed with severe preeclampsia. In the group of women with preeclampsia, there were 51 patients with adequate for gestational age foetal growth and 64 patients with the foetal growth restriction in the course of severe preeclampsia. The control group consisted of 65 healthy patients with normal pregnancy course, with no cardiovascular disorders at the present and in the history, normal blood pressure and normal intrauterine foetal growth. Matrix metalloproteinase-3 (MMP-3) in maternal circulation were determined by ELISA method. Results: In our studies, we observed elevated levels of matrix metalloproteinase-3 in preeclamptic women with pregnancies complicated by FGR and significantly lower in the group of normotensive women with idiopathic FGR. The mean values of MMP-3 were 33.50 ± 65.74 ng/mL [Median (min-max) 19.19 (2.05-454.53)] in the Control group, 21.22 ± 23.28 ng/mL [Median (min-max) 16.39 (3.45-156.29)] in the FGR group, 35.96 ± 46.14 ng/mL [Median (min-max) 25.21 (4.16-253.05)] in the P group and 52.81 ± 61.61 ng/mL [Median (min-max) 32.83 (5.06-314.14)] in preeclamptic women with FGR (group PI) respectively.The assessment of MMP-3 in the serum of women with pregnancies complicated by intrauterine foetal growth restriction with normal values of blood pressure and in the group of preeclamptic patients in relation to healthy pregnant women with uncomplicated pregnancies and in relation to preeclamptic patients with normal intrauterine foetal growth is the novelty of this study. Such a strict definition of each research group seems to allow for the assessment of each pregnancy complication separately. Conclusion: It seems that higher levels of MMP-3 in preeclamptic women may suggest the need for observation towards the risk of lower birth weight of newborns. This necessitates further research and a better integration in the clinical practice.

Integrated growth assessment in the first 1000 d of life: an interdisciplinary conceptual framework.

OBJECTIVES: Prenatal growth affects short- and long-term morbidity, mortality and growth, yet communication between prenatal and postnatal healthcare teams is often minimal. This paper aims to develop an integrated, interdisciplinary framework for foetal/infant growth assessment, contributing to the continuity of care across the first 1000 d of life. DESIGN: A multidisciplinary think-tank met regularly over many months to share and debate their practice and research experience related to foetal/infant growth assessment. Participants' personal practice and knowledge were verified against and supplemented by published research. SETTING: Online and in-person brainstorming sessions of growth assessment practices that are feasible and valuable in resource-limited, low- and middle-income country (LMIC) settings. PARTICIPANTS: A group of obstetricians, paediatricians, dietitians/nutritionists and a statistician. RESULTS: Numerous measurements, indices and indicators were identified for growth assessment in the first 1000 d. Relationships between foetal, neonatal and infant measurements were elucidated and integrated into an interdisciplinary framework. Practices relevant to LMIC were then highlighted: antenatal Doppler screening, comprehensive and accurate birth anthropometry (including proportionality of weight, length and head circumference), placenta weighing and incorporation of length-for-age, weight-for-length and mid-upper arm circumference in routine growth monitoring. The need for appropriate, standardised clinical records and corresponding policies to guide clinical practice and facilitate interdisciplinary communication over time became apparent. CONCLUSIONS: Clearer communication between prenatal, perinatal and postnatal health care providers, within the framework of a common understanding of growth assessment and a supportive policy environment, is a prerequisite to continuity of care and optimal health and development outcomes.

Vitamin D in pregnancy (GRAVITD) - a randomised controlled trial identifying associations and mechanisms linking maternal Vitamin D deficiency to placental dysfunction and adverse pregnancy outcomes - study protocol.

BACKGROUND: The prevalence of vitamin D deficiency is high among pregnant women. Vitamin D deficiency in pregnancy is associated with increased risk of adverse pregnancy outcomes especially complications related to placental dysfunction and insulin resistance. The objective of this study is to investigate if a higher dose of vitamin D supplementation in pregnancy reduces the prevalence of vitamin D deficiency and prevents adverse pregnancy outcome with special emphasize on preeclampsia, foetal growth restriction and gestational diabetes. METHODS: GRAVITD is a double-blinded randomised trial with parallel groups where all pregnant women attending the free of charge national nuchal translucency scan programme in gestational week 10-14 at Randers Regional Hospital are invited to participate. Enrolment started in June 2020. Participants are randomised in a two armed randomization with a 1:1 allocation ratio into 1) control group - receives 10 µg of vitamin D or 2) intervention group - receives 90 µg of vitamin D. A total of 2000 pregnant women will be included. Maternal blood samples and questionnaires describing life-style habits are collected upon enrolment. For half of the participants blood samples and questionnaires will be repeated again in 3rd trimester. Blood samples will be analysed for 25-hydroxy-vitamin D using high-performance liquid chromatography coupled with tandem mass spectrometry. Upon delivery, placental tissue and umbilicalcord blood will be collected and information on maternal and fetal outcomes will be exstracted from medical records. The primary outcomes are serum levels of 25-hydroxy-vitamin D ≥ 75 nmol/L and the rate of preeclampsia, foetal growth restriction and gestational diabetes. Secondary outcome includes identification and impact on placental functions related to vitamin D. A tertiary outcome is to initiate a cohort of children born from mothers in the trial for future follow-up of the effects of vitamin D on childhood health. DISCUSSION: Provided that this trial finds beneficial effects of a higher dose of vitamin D supplementation in pregnancies, official recommendations can be adjusted accordingly. This will provide a low-cost and easily implementable adjustment of prenatal care which can improve health for both mother and child during pregnancy and beyond. TRIAL REGISTRATION: ClinicalTrial.gov: NCT04291313 . Registered February 17, 2020.

Epigenetic control of the imprinted growth regulator Cdkn1c in cadmium-induced placental dysfunction.

Cadmium (Cd) is a toxic metal ubiquitous in the environment. In utero, Cd is inefficiently transported to the foetus but causes foetal growth restriction (FGR), likely through impairment of the placenta where Cd accumulates. However, the underlying molecular mechanisms are poorly understood. Cd can modulate the expression of imprinted genes, defined by their transcription from one parental allele, which play critical roles in placental and foetal growth. The expression of imprinted genes is governed by DNA methylation at Imprinting Control Regions (ICRs), which are susceptible to environmental perturbation. The imprinted gene Cdkn1c/CDKN1C is a major regulator of placental development, is implicated in FGR, and shows increased expression in response to Cd exposure in mice. Here, we use a hybrid mouse model of in utero Cd exposure to determine if the increase in placental Cdkn1c expression is caused by changes to ICR DNA methylation and loss of imprinting (LOI). Consistent with prior studies, Cd causes FGR and impacts placental structure and Cdkn1c expression at late gestation. Using polymorphisms to distinguish parental alleles, we demonstrate that increased Cdkn1c expression is not driven by changes to DNA methylation or LOI. We show that Cdkn1c is expressed primarily in the placental labyrinth which is proportionally increased in size in response to Cd. We conclude that the Cd-associated increase in Cdkn1c expression can be fully explained by alterations to placental structure. These results have implications for understanding mechanisms of Cd-induced placental dysfunction and, more broadly, for the study of FGR associated with increased Cdkn1c/CDKN1C expression.

Risk factors and foetal growth restriction associated with expectant treatment of early-onset preeclampsia.

OBJECTIVE: To identify the factors affecting expectant management of early-onset preeclampsia, and evaluate the correlation between expectant treatment and foetal growth restriction. MATERIALS AND METHODS: The retrospective study included 72 women who were admitted for early-onset preeclampsia between February 2018 to April 2021. Data included maternal clinical parameters, demographic and maternal and neonatal outcomes, which were analysed for correlation. RESULTS: Multiple logistic regression analysis demonstrated that the time interval from the onset of 24-h proteinuria to termination of pregnancy showed a strong correlation with the expectant treatment; Univariate logistic analysis confirmed that there was no correlation between expectant treatment and foetal growth restriction. CONCLUSION: There was a negative correlation between the duration of 24-h proteinuria and the expectant treatment of patients with early-onset preeclampsia; Expectant treatment could not improve the development of foetal growth restriction in patients with early-onset preeclampsia.KEY MESSAGESThe duration of 24-h proteinuria affects the effectiveness of expectant management of early-onset preeclampsia.Expectant management can reduce adverse neonatal outcomes due to iatrogenic preterm delivery, but it cannot improve the occurrence of foetal growth restriction.