Fetal Growth Velocity-A Breakthrough in Intrauterine Growth Assessment?

The pursuit of assessing fetal well-being in obstetrical practice remains a central tenet, propelling ongoing endeavors to explore innovative markers and diagnostic methodologies aimed at prognosing potential perinatal adversities. Deviations from standard patterns of intrauterine growth, whether exhibiting excessive or insufficient trajectories, stand as pivotal indices hinting at underlying pathophysiological processes or heightened concurrent medical conditions. Initiatives like the Delphi consensus and the INTERGROWTH-21st project strive to refine diagnostic criteria and establish international standards for fetal growth assessment. This article aims to present the current knowledge regarding the assessment of abnormal growth, including novel methods such as growth velocity. Integrating fetal growth velocity assessment into perinatal care protocols holds promise in enhancing diagnostic precision. Growth velocity, involving changes in fetal size over a given period, offers insights into distinguishing between constitutional and pathological growth abnormalities. Various methodologies and models have been proposed to evaluate growth velocity, with notable advancements in understanding fetal growth patterns across different trimesters. It is believed that accelerated and reduced growth velocity may be a sensible parameter in the detection of fetal growth restriction (FGR), small-for-gestational-age (SGA) fetuses, large-for-gestational-age (LGA) fetuses and macrosomic fetuses as well as appropriate-for-gestational age (AGA) fetuses that encounter problems with growth continuation. Recent studies found that changes in growth velocity reflect the risk of adverse perinatal outcomes (APOs). Future directions in fetal health research aim to elucidate the long-term consequences of abnormal fetal growth velocity on neurodevelopmental outcomes, highlighting the critical role of early assessment and intervention.

Wound Microbiota and Its Impact on Wound Healing.

Wound healing is a complex process influenced by age, systemic conditions, and local factors. The wound microbiota's crucial role in this process is gaining recognition. This concise review outlines wound microbiota impacts on healing, emphasizing distinct phases like hemostasis, inflammation, and cell proliferation. Inflammatory responses, orchestrated by growth factors and cytokines, recruit neutrophils and monocytes to eliminate pathogens and debris. Notably, microbiota alterations relate to changes in wound healing dynamics. Commensal bacteria influence immune responses, keratinocyte growth, and blood vessel development. For instance, Staphylococcus epidermidis aids keratinocyte progression, while Staphylococcus aureus colonization impedes healing. Other bacteria like Group A Streptococcus spp. And Pseudomonas affect wound healing as well. Clinical applications of microbiota-based wound care are promising, with probiotics and specific bacteria like Acinetobacter baumannii aiding tissue repair through molecule secretion. Understanding microbiota influence on wound healing offers therapeutic avenues. Tailored approaches, including probiotics, prebiotics, and antibiotics, can manipulate the microbiota to enhance immune modulation, tissue repair, and inflammation control. Despite progress, critical questions linger. Determining the ideal microbiota composition for optimal wound healing, elucidating precise influence mechanisms, devising effective manipulation strategies, and comprehending the intricate interplay between the microbiota, host, and other factors require further exploration.

Molecular Pathways of Altered Brain Development in Fetuses Exposed to Hypoxia.

Perinatal hypoxia is a major cause of neurodevelopmental impairment and subsequent motor and cognitive dysfunctions; it is associated with fetal growth restriction and uteroplacental dysfunction during pregnancy. This review aims to present the current knowledge on brain development resulting from perinatal asphyxia, including the causes, symptoms, and means of predicting the degree of brain damage. Furthermore, this review discusses the specificity of brain development in the growth-restricted fetus and how it is replicated and studied in animal models. Finally, this review aims at identifying the least understood and missing molecular pathways of abnormal brain development, especially with respect to potential treatment intervention.

Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application, COSA): study protocol for a multicentre, non-blinded, randomised controlled trial.

INTRODUCTION: Cervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation. METHODS AND ANALYSIS: This trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78. ETHICS AND DISSEMINATION: The study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal. TRIAL REGISTRATION: NCT05268640.

Large-for-gestational-age or macrosomia as a classifier for risk of adverse perinatal outcome: a retrospective cross-sectional study.

OBJECTIVE: Small for gestational age (SGA) fetuses and neonates are of great interest, while those who are too big are much less studied. The aim was to analyze the classifiers described by ACOG "Fetal macrosomia" practice bulletin as predictors of adverse perinatal outcomes for overgrown fetuses and their mothers. MATERIALS: From a database of 53,586 singleton term births, appropriate-for-gestational-age (AGA), large for gestational age (LGA), and macrosomic deliveries were selected. AGA served as a control. The crude and adjusted odds ratios (aORs) were calculated for large-for-gestational-age >90th centile, and macrosomia >4000 g, >4250 g, and >4500 g. Patients with and without diabetes were analyzed separately. RESULTS: Macrosomia >4000 g performed poorer than other classifiers. LGA performed comparably to other definitions of macrosomia. Diabetes carries a severe risk of complications for overgrown neonates, but those non-diabetic also have increased risk. CONCLUSIONS: Definition of macrosomia as weight >4000 g should be reconsidered. LGA >90th centile should be used as a definition of fetal overgrowth along with other definitions of macrosomia.

Is growth restriction in twin pregnancies a double challenge? - A narrative review.

BACKGROUND: Foetal growth restriction (FGR) complicates about 25-47% of twin pregnancies. One or both foetuses can be restricted. Pregnancies with discordant growth of foetuses are associated with a sevenfold increased risk of neonatal morbidity. MATERIALS AND METHODS: This is a narrative or traditional literature review. A literature search was performed to present a comprehensive, critical and objective analysis of the current knowledge on growth restriction in twin pregnancies. RESULTS: The definitions of FGR in twin pregnancies and selective FGR (sFGR) differ between international societies. In 2019, the Delphi procedure aimed to unify the definitions of sFGR in twin pregnancies. Several growth charts for twins have been published. However, most societies recommend singleton growth charts as better in detecting hypoxic complications of FGR in twin pregnancies. Discordant growth in twins results from placental insufficiency, congenital anomalies, chromosomal aberrations and TORCH infections. CONCLUSIONS: Definitions and management of sFGR depend on chorionicity. The management aims to protect the properly growing foetus from ischemic complications or in utero death. In most cases, expectant management, strict surveillance and preterm labour are the methods of choice. Due to the co-existence of properly growing and small foetuses in one uterus, determining the appropriate time for delivery is challenging. In the case of preterm labour, even late preterm, antenatal corticosteroid therapy (ACT) in FGR twin pregnancies is beneficial because it decreases neonatal morbidity.

Growth Abnormalities as a Risk Factor of Adverse Neonatal Outcome in Hypertensive Pregnancies-A Single-Center Retrospective Cohort Study.

(1) Background: Hypertensive disorders of pregnancy (HDP) include gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE), and preeclampsia superimposed on chronic hypertension (CH with PE). HDP is associated with several short and long-term perinatal and neonatal complications, such as newborn growth restriction and death. This study aimed to establish the association between HDP, newborn growth abnormalities, and neonatal outcome. (2) Methods: This is a single-center retrospective cohort study of 63651 singleton deliveries. (3) Results: Univariate analysis showed a significantly increased risk of intrauterine and neonatal death associated with maternal hypertension and growth disorders. There were differences between growth charts used, with the highest risk of stillbirth for SGA defined by the Intergrowth chart (OR 17.2) and neonatal death for newborn growth restriction (NGR) based on Intergrowth (OR 19.1). Multivariate analysis showed that NGR is a stronger risk factor of neonatal death than SGA only. (4) Conclusions: HDP is significantly associated with growth abnormalities and is an independent risk factor of adverse outcomes. The presence of newborn growth restriction is strongly associated with the risk of neonatal death. The choice of growth chart has a substantial effect on the percentage of diagnosis of SGA and NGR.

Compliance with gestational weight gain recommendations in a cross-sectional study of term pregnancies - how far reality falls from the standard?

OBJECTIVES: During pregnancy, two aspects are critical in the context of adverse perinatal outcomes (APO): preconception obesity and gestational weight gain. This study aimed to assess compliance with the 2009 IOM guidelines, compare GWG with and without correcting for gestation duration, and observe the relationship between pre-pregnancy BMI and GWG and neonatal birth weight. MATERIAL AND METHODS: This is a cross-sectional study conducted from 2015-2018 at the St. Sophia's Specialist Hospital in Warsaw, Poland. Self-reported pre-pregnancy and predelivery weight were collected. RESULTS: The presented data set amounts to 7820 records. Analysis of weight gain compliance with IOM recommendations showed that only 41-44% (depending on the calculation method) of women had weight gain in accordance with IOM guidelines (22-23% - below; 33-37% - above). Overweight and obese women with diabetes are more likely to comply with IOM than women without diabetes. In contrast, women with normal-weight and underweight with diabetes are less likely to achieve IOM weight gain in pregnancy than women without diabetes. Women who have GWG below recommendations significantly more often gave birth to SGA neonates, and women who exceeded GWG standards significantly more often gave birth to LGA neonates. CONCLUSIONS: Less than half of women had GWG within the recommended norms. Statistically significant differences were found in methods of calculation of GWG, but it was not found clinically significant. Correction for pregnancy duration when calculating GWG reclassifies two percent of patients. We underestimate the risk of crossing the line between overweight and obesity during pregnancy.

Fetal Growth Diagnosis and Management among Perinatal Medical Professionals: A Survey of Practice and Literature Review.

INTRODUCTION: This paper aimed to assess the knowledge of healthcare professionals (obstetric and gynecology residents, specialists, and midwives) in the field of perinatal medicine regarding fetal growth diagnosis and management. METHODS: A questionnaire was created consisting of a set of questions regarding demographic data, methods of growth assessment, and management. It was a handout survey. The results were analyzed with the use of descriptive statistics and χ2 analysis using the program Statistica. RESULTS: 190 medical professionals have participated in the questionnaire. 86.3% of respondents agreed that pregnancy dating should be modified based on first-trimester ultrasound. 90.9% agreed that III trimester ultrasound has a ±15% margin of error. When asked which growth charts are best fit for assessing growth in a studied population, 10.7% marked standard, 37.4% reference, 26.2% customized, and 26.2% did not know the difference between the three choices. 60.3% stated that they use a growth chart to assess growth and qualify fetuses for monitoring. 70.2% used the 10th centile as a cutoff, 20.1% 5th centile, and 9.7% 3rd centile. Only 40.9% would diagnose fetal growth restriction based on fetal weight only. 28.7% using the 10th centile cutoff, 16.1% 5th centile, and 54.0% 3rd centile. Only a quarter of the respondents were able to name the growth chart or tool that they use for assessment. The most common responses were Yudkin, Hadlock, and online calculators of Fetal Medicina Barcelona and the Fetal Medicine Foundation. DISCUSSION: A lot of confusion is observed primarily in the aspect of cutoff values for identification, subsequent monitoring, and management of fetal growth restriction. There is a need for extensive training and education in this field and uniform national recommendations.

A unique case of diagnosis of a heterotopic pregnancy at 26 weeks - case report and literature review.

BACKGROUND: Heterotopic pregnancy (HP) is a rare condition when at least two pregnancies are present simultaneously at different implantation sites and only one located in the uterine cavity. The majority of cases are diagnosed in the first trimester. CASE PRESENTATION: We present a unique case of HP diagnosed at 26 weeks of spontaneous pregnancy in a patient without any relevant risk factors. We performed an extensive review of HP cases from MEDLINE (PUBMED) published in English between 2005-2019 to prove this case's uniqueness. A 24-year-old woman presented because of threatened preterm birth. Despite treatment, pain aggravated, without progression of labor. An emergency ultrasound exam revealed free fluid in the abdominal cavity. Suspicion of active bleeding prompted the medical team to perform an exploratory laparotomy. The surgery team found a ruptured heterotopic pregnancy. This was an unexpected cause of nontraumatic hemoperitoneum at such advanced gestational age. The postoperative period was uneventful, and the intrauterine pregnancy continued to term. The final review included 86 out of 124 records. A total number of 509 cases were identified, but not all of them had complete data. The maximum reported gestational age at the time of diagnosis was 16 weeks of pregnancy, while our case became symptomatic and was diagnosed at 26 weeks of pregnancy. CONCLUSIONS: Regardless of pregnancy age, HP can be a cause of hemoperitoneum, and it should be included in the differential diagnosis of acute abdomen in the second trimester.

Uterine Artery Doppler Reference Ranges in a Twin Caucasian Population Followed Longitudinally From 17 to 37 Weeks Gestation Compared to That of Singletons.

OBJECTIVES: The primary aim was to measure uterine artery (UtA) indices in twin pregnancies of Polish Caucasian women and compare it with a previously published study by Geipel et al for DC twins (2011). The secondary aim was to find differences in UtA indices in MC, DC twins, and singletons. METHODS: A prospective longitudinal evaluation of UtA Doppler indices in 1462 examinations of twins and 5766 examinations of singletons between 17 and 37 gestational age (GA). Pulsatility index (PI) and resistance index (RI) were calculated. RESULTS: UtA PI and RI are lower in the twins than singletons but the analyzed mean values throughout gestation are higher than the study presented by Geipel et al. Obtained curves for DC twins and singletons had the same form as Geipel's curves. In MC twins, curves are flatter and characterized by lower differences throughout pregnancy than Geipel's curves for DC twins. They tend to be more similar about 32 weeks of gestations, resulting from different placenta structure in MC than DC twin pregnancies. CONCLUSIONS: UtA Doppler indices in twin pregnancies are lower than in singletons. Obtained data have higher values for twins than reference charts proposed by Geipel's for dichorionic twins. We observed some differences between monochorionic and dichorionic twins' curves throughout pregnancy, but they were not significant.

Development of birth weight for gestational age charts and comparison with currently used charts: defining growth in the Polish population.

OBJECTIVES: This study aimed to obtain the reference curves of birth weight for gestational age percentiles for the Polish population and to compare them to published charts in terms of detected proportions of small for gestational age (SGA) and large for gestational age (LGA). METHODS: The reference curves of birth weight from 24 to 42 weeks of gestation were computed based on 39,092 singleton deliveries. The nomograms included the 3rd to the 97th percentiles and standard deviations. The percentiles were calculated for female and male newborns. The theoretical and true proportions of percentiles for the studied population were estimated based on six growth charts (Fenton, Intergrowth Project, global reference chart, Yudkin, Dubiel, and the World Health Organization chart). RESULTS: The 50th percentile male and female newborns at 40 weeks weighed 3645.8 and 3486.7 g, respectively. The difference was 159.1 g. The ranges between the 3rd and 97th percentile at 40 weeks were 1481.5 g for males and 1423.5 for females. A total of 9.8% SGA and 10.27% LGA were defined, higher than that identified using the Fenton chart and even higher than that identified using the Intergrowth Project. CONCLUSION: Population growth charts identify more newborns with abnormal growth (both LGA and SGA). The similarity between charts in LGA above the 95th percentile is observed. The discrepancies in SGA are significantly greater, specifically in preterm births than in term births. Similar coverage is found in term pregnancies, regardless of birth weight for gestational age or intrauterine charts. The feasibility of a Polish population growth chart needs to be validated for predicting adverse perinatal outcomes.

Successful pregnancy in women with inferior vena cava stenosis - case report and discussion.

OBJECTIVES: Inferior vena cava syndrome (IVCS) is a heterogenous group of symptoms resulting in obstruction of the main vein inflow . Common reasons are thrombotic changes and tumors. Incidence of inferior vena cava (IVC) anomalies is 0.3% in general population. Iatrogenic IVC lesions caused by catheter insertion play increasing role. Treatment varies depending on the condition. MATERIAL AND METHODS: 32-year old patient was diagnosed with IVC stenosis during infertility related preconception evaluation and informed about increased risk in planned pregnancy. Throughout the well progressing pregnancy patient received low molecular weight heparin. RESULTS: The diagnosis was confirmed intraoperatively during the planned cesarean section. Early postpartum period was normal and patient was discharged with antithrombotic prophylaxis. CONCLUSIONS: Isolated IVC stenosis in pregnancy has not been yet reported in medical literature. Even though IVC anomalies may be associated with other congenital changes, in this case the central venous line treatment in infancy seems to be the most likely cause. Malformations are often accidentally diagnosed because patients are usually asymptomatic. CT and MRI are recommended diagnostic tools. Conservative treatment is recommended for asymptomatic patients, as opposed to surgical treatment for symptomatic. However, due to condition's rarity, there is no evidence based approach management.

Foetal goitrous hypothyroidism - easy to recognise, difficult to treat. Is combined intra-amniotic and intravenous L-thyroxine therapy an option?

INTRODUCTION: Foetal hypothyroidism negatively impacts somatic and neurological child development and can be the cause of serious obstetric and perinatal complications. We present a rare case of a large foetal dyshormonogenetic goitre, causing foetal neck hyperexten-sion, oesophageal compression, and cardiac high-output failure. MATERIAL AND METHODS: A foetal goitre complicated by cardiomegaly and polyhydramnios was diagnosed at 23 weeks of gestation (WG) on a routine ultrasonographic (US) assessment in a healthy nullipara. Foetal blood sampling was performed and a severe foetal hypothyroid-ism was diagnosed. Treatment was undertaken with an intra-amniotic followed by combined intra-amniotic and intravenous injections of L-thyroxine (L-T4). A total of 11 doses of L-T4 were administered between 24-37 WG to the foetus. RESULTS: A complete regression of foetal goitre, cardiomegaly, and polyhydramnios was observed. At 38 WG the patient delivered vagi-nally a male infant with mild hypothyroidism and no signs of goitre or cardiomegaly on postnatal US. Neurological development of the one year old baby is normal. CONCLUSIONS: The effective diminishing of serum TSH concentration and goitre size was reached after combined intra-amniotic and in-travenous L-T4 injections were given. L-T4 requirement in the foetus is equal to or above 15 µg/kg daily and should be given in weekly intervals due to its rapid metabolism by the foetus and by placental type 3 deiodinase. Intra-amniotic L-T4 administration may be inef-fective when a large goitre indisposes amniotic fluid swallowing by the foetus, so then the combined L-T4 injections into the umbilical vein and intra-amniotically in experienced hands seems to be a reasonable and effective option.