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Intracranial hemorrhage (ICH) in pregnancy, estimated at 1 in 10,000 cases, presents significant diagnostic challenges prenatally despite advanced imaging techniques such as ultrasonography (US) and magnetic resonance imaging (MRI). Detecting ICH is crucial for pregnancy management and future treatment decisions aimed at improving fetal survival and reducing brain damage. This report presents the diagnosis and outcomes of 2 cases of prenatal ICH. The first case involves a 30-year-old pregnant woman with irregular prenatal care diagnosed with ICH at 32 weeks of gestation via US and MRI. She chose to continue the pregnancy, delivering a 3160 g male infant at 36 weeks via cesarean section. Following NICU care including resuscitation and ventriculoperitoneal shunt placement, the infant was discharged. Subsequent examinations showed a reduction in ventricle size. In the second case, a 27-year-old woman taking acenocoumarol for a mechanical heart valve developed fetal subdural hemorrhage detected by US and MRI. She opted to terminate the pregnancy, resulting in a stillborn male infant weighing 1530 g. Fetal ICH presents with varying severity and prognostic implications, diagnosed and graded using US. Fetal cranial MRI may help clarify the etiology. Management remains controversial, with termination of pregnancy potentially warranted in severe cases due to poor prognosis. Further research is needed to refine management and improve outcomes in fetal ICH.

We analyzed and compared variations in the urinary metabolome, as well as postnatal clinical outcomes among preterm infants, based on the timing of antenatal corticosteroid (ACS) administration in response to preterm labor onset in their mothers. This was a prospective observational study held in the Neonatal Intensive Care Unit, Department of Woman's and Child's Health, Padova University Hospital (Italy). A urine sample was obtained from each patient within 24 h of birth; Mass Spectrometry-based untargeted metabolomics analysis was then conducted. We searched for any significant disparities in the metabolomic profile of preterm newborns subjected to antenatal corticosteroid (ACS) treatment at varying timings; their correlation with clinical outcomes were also evaluated. The group receiving ACS within the optimal time window (1–7 days before delivery) exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid, coupled with a decrease in pipecolic acid. Clinically, this group demonstrated a reduced need for invasive ventilation (p = 0.04). In conclusion, metabolomics analysis identified several metabolites that discriminated preterm infants whose mothers received ACS within the recommended time window. Elevated levels of cysteine and 5-Hydroxyindoleacetic acid, metabolites characterized by antioxidant and anti-inflammatory properties, were observed in these infants. This metabolic profile correlated with improved respiratory outcomes, as evidenced by a reduced necessity for invasive ventilation at birth. [ABSTRACT FROM AUTHOR]

• Prenatal diagnosis is an important issue in cases like pelvic kidney because early detection can give the opportunity for anatomic and genetic screening for related anomalies. • Pelvic kidneys could be diagnosed in the early prenatal period. • Postnatal follow-up should be performed closely for the assessment of renal functions. Evaluation of demographic characteristics and postnatal outcomes of patients with suspected fetal pelvic kidney diagnosis followed in a tertiary center. This retrospective study was conducted in Ankara Bilkent City Hospital perinatology clinic between 2020–2023. Demographic features, prenatal ultrasound findings, and postnatal outcomes were reported. Pelvic kidney localization was on the left in 11(55 %) patients, on the right in 7(35 %), and bilateral in 2(10 %) patients in prenatal ultrasonography. The gender of the 12(60 %) fetuses were male and 8(40 %) of them were female. The pelvic kidney was an isolated finding in 8(40 %) fetuses, additional findings were present in the remaining 12(60 %) fetuses. Pelvic kidney was confirmed postnatally by ultrasound in all 18 fetuses. However two cases with prenatal ultrasound findings resulted in intrauterine fetal demise and the final diagnosis could not be confirmed as the parents refused autopsia. Cases were divided into 3 groups according to postnatal follow-up duration as 0–12 months (n = 7), 12–24 months (n = 7) and 24–44 months (n = 4). Atrial septal defect was the most common accompanying abnormality in the postnatal period (n = 4). Smaller kidney size (n = 7), vesicoureteral reflux (n = 3), and impaired renal function (n = 3) were the most common postnatal complications. Pelvic kidney can be diagnosed in fetal abnormality screening ultrasound and postnatal follow-up should be performed closely for the assessment of renal functions. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study aimed to assess the role of fetal echocardiography in detecting congenital heart diseases (CHDs) prenatally and its impact on the incidence of CHDs among newborns. Methods: A total of 200 pregnant women undergoing fetal echocardiography for suspected CHDs were included. Demographic data were collected, and prenatal and postnatal outcomes were analyzed. Diagnostic accuracy of fetal echocardiography was assessed by comparing prenatal findings with postnatal echocardiograms or autopsy reports. Results: Fetal echocardiography identified 50 cases of CHDs prenatally, with ventricular septal defects (VSDs) and atrial septal defects (ASDs) being the most common anomalies. The incidence rate of CHDs among newborns was 40 per 1000 live births. Postnatally, the majority of infants underwent surgical intervention shortly after birth. Conclusion: Fetal echocardiography plays a crucial role in prenatal detection of CHDs, enabling early interventions and optimizing outcomes for affected infants. Continued efforts to enhance prenatal screening protocols and multidisciplinary collaboration are essential to improve the diagnosis and management of CHDs. [ABSTRACT FROM AUTHOR]

Abstract Background Advances in postnatal care for hemolytic disease of the fetus and newborn (HDFN) have occurred over the past decades, but little is known regarding the frequency of postnatal treatment and the clinical outcomes of affected neonates. Most studies reporting on HDFN originate from high-income countries or relatively large centers, but important differences between centers and countries may exist due to differences in prevalence and available treatment options. We therefore aimed to evaluate the postnatal treatment landscape and clinical outcomes in neonates with Rhesus factor D (Rh(D))- and/or K-mediated HDFN and to provide recommendations for future research. Methods We conducted a rapid literature review of case reports and series, observational retrospective and prospective cohort studies, and trials describing pregnancies or children affected by Rh(D)- or K-mediated HDFN published between 2005 and 2021. Information relevant to the treatment of HDFN and clinical outcomes was extracted. Medline, ClinicalTrials.gov and EMBASE were searched for relevant studies by two independent reviewers through title/abstract and full-text screening. Two independent reviewers extracted data and assessed methodological quality of included studies. Results Forty-three studies reporting postnatal data were included. The median frequency of exchange transfusions was 6.0% [interquartile range (IQR): 0.0–20.0] in K-mediated HDFN and 26.5% [IQR: 18.0–42.9] in Rh(D)-mediated HDFN. The median use of simple red blood cell transfusions in K-mediated HDFN was 50.0% [IQR: 25.0–56.0] and 60.0% [IQR: 20.0–72.0] in Rh(D)-mediated HDFN. Large differences in transfusion rates were found between centers. Neonatal mortality amongst cases treated with intrauterine transfusion(s) was 1.2% [IQR: 0–4.4]. Guidelines and thresholds for exchange transfusions and simple RBC transfusions were reported in 50% of studies. Conclusion Most included studies were from middle- to high-income countries. No studies with a higher level of evidence from centers in low-income countries were available. We noted a shortage and inconsistency in the reporting of relevant data and provide recommendations for future reports. Although large variations between studies was found and information was often missing, analysis showed that the postnatal burden of HDFN, including need for neonatal interventions, remains high. Systematic review registration PROSPERO 2021 CRD42021234940. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021234940 .

This document discusses the challenges and management of prenatal counseling for DGUOK deficiency, a mitochondrial disease. The authors emphasize the importance of accurate information and strong support for parents and families following a prenatal diagnosis. They highlight the need for a multidisciplinary approach involving various healthcare professionals. The document also mentions the lack of clear genotype-phenotype correlation in patients with pathogenic missense variants in the DGUOK gene. Overall, the authors stress the need for more research and comprehensive information to guide healthcare providers in counseling families about DGUOK deficiency. [Extracted from the article]

Background: Advances in postnatal care for hemolytic disease of the fetus and newborn (HDFN) have occurred over the past decades, but little is known regarding the frequency of postnatal treatment and the clinical outcomes of affected neonates. Most studies reporting on HDFN originate from high-income countries or relatively large centers, but important differences between centers and countries may exist due to differences in prevalence and available treatment options. We therefore aimed to evaluate the postnatal treatment landscape and clinical outcomes in neonates with Rhesus factor D (Rh(D))- and/or K-mediated HDFN and to provide recommendations for future research. Methods: We conducted a rapid literature review of case reports and series, observational retrospective and prospective cohort studies, and trials describing pregnancies or children affected by Rh(D)- or K-mediated HDFN published between 2005 and 2021. Information relevant to the treatment of HDFN and clinical outcomes was extracted. Medline, ClinicalTrials.gov and EMBASE were searched for relevant studies by two independent reviewers through title/abstract and full-text screening. Two independent reviewers extracted data and assessed methodological quality of included studies. Results: Forty-three studies reporting postnatal data were included. The median frequency of exchange transfusions was 6.0% [interquartile range (IQR): 0.0–20.0] in K-mediated HDFN and 26.5% [IQR: 18.0–42.9] in Rh(D)-mediated HDFN. The median use of simple red blood cell transfusions in K-mediated HDFN was 50.0% [IQR: 25.0–56.0] and 60.0% [IQR: 20.0–72.0] in Rh(D)-mediated HDFN. Large differences in transfusion rates were found between centers. Neonatal mortality amongst cases treated with intrauterine transfusion(s) was 1.2% [IQR: 0–4.4]. Guidelines and thresholds for exchange transfusions and simple RBC transfusions were reported in 50% of studies. Conclusion: Most included studies were from middle- to high-income countries. No studies with a higher level of evidence from centers in low-income countries were available. We noted a shortage and inconsistency in the reporting of relevant data and provide recommendations for future reports. Although large variations between studies was found and information was often missing, analysis showed that the postnatal burden of HDFN, including need for neonatal interventions, remains high. Systematic review registration: PROSPERO 2021 CRD42021234940. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021234940. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the antenatal, perinatal, and postnatal outcomes of congenital lung malformations (CLM) diagnosed prenatally. Methods: This was a retrospective cross-sectional study evaluating prenatally diagnosed CLMs. Prenatal findings such as diagnosis weeks, additional anomalies, karyotype results, and pregnancy outcomes of the cases were collected from the hospital digital record system. The data of the postnatal long-term course and outcomes of the cases were obtained by contacting the parents by telephone. Results: Forty-seven CLM cases were included in the study. 12.8% of the cases had structural anomalies. Chromosome analysis was performed on 8 (17%) cases and all of them had a normal karyotype. Forty-four (93.7%) cases had a live birth. 19.1% of the cases gave birth prematurely. The newborns had low APGAR scores (

We analyzed and compared variations in the urinary metabolome, as well as postnatal clinical outcomes among preterm infants, based on the timing of antenatal corticosteroid (ACS) administration in response to preterm labor onset in their mothers. This was a prospective observational study held in the Neonatal Intensive Care Unit, Department of Woman’s and Child’s Health, Padova University Hospital (Italy). A urine sample was obtained from each patient within 24 h of birth; Mass Spectrometry-based untargeted metabolomics analysis was then conducted. We searched for any significant disparities in the metabolomic profile of preterm newborns subjected to antenatal corticosteroid (ACS) treatment at varying timings; their correlation with clinical outcomes were also evaluated. The group receiving ACS within the optimal time window (1–7 days before delivery) exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid, coupled with a decrease in pipecolic acid. Clinically, this group demonstrated a reduced need for invasive ventilation (p = 0.04). In conclusion, metabolomics analysis identified several metabolites that discriminated preterm infants whose mothers received ACS within the recommended time window. Elevated levels of cysteine and 5-Hydroxyindoleacetic acid, metabolites characterized by antioxidant and anti-inflammatory properties, were observed in these infants. This metabolic profile correlated with improved respiratory outcomes, as evidenced by a reduced necessity for invasive ventilation at birth.

Background: Pre-pregnancy overweight and obesity in reproductive-aged women becomes a growing tendency in middle- and high-income populations. This study aimed to evaluate whether maternal excess body mass index (BMI) before gestation is associated with children's anthropometric characteristics, as well as perinatal and postnatal outcomes. Methods: This was a cross-sectional study performed on 5198 children aged 2–5 years old and their paired mothers, assigned from 9 different areas of Greece. Maternal and childhood anthropometric data, as well as perinatal and postnatal outcomes, were collected from medical history records or validated questionnaires. Results: Prevalences of 24.4% and 30.6% of overweight/obesity were recorded for the enrolled children and their mothers 2–5 years postpartum. Maternal pre-pregnancy overweight/obesity was more frequently observed in older mothers and female children, and was also associated with high childbirth weight, preterm birth, high newborn ponderal index, caesarean section delivery, diabetes type 1, and childhood overweight/obesity at pre-school age. In multivariate analysis, maternal pre-pregnancy overweight/obesity was independently associated with a higher risk of childhood overweight/obesity at pre-school age, as well as with a higher increased incidence of childbirth weight, caesarean section delivery, and diabetes type 1. Conclusions: Maternal overweight/obesity rates before gestation were related with increased childhood weight status at birth and 2–5 years postpartum, highlighting the necessity of encouraging healthy lifestyle promotion, including healthier nutritional habits, and focusing on obesity population policies and nutritional interventions among women of reproductive age. [ABSTRACT FROM AUTHOR]

Objective Heterotaxy syndrome (HS) is often associated with complex congenital heart disease (CHD). While fetal echocardiography (FE) permits accurate prenatal identification of most CHD, the high level of disease complexity in HS may pose challenges in predicting postnatal findings and outcomes. This study aimed to define the accuracy of FE in predicting postnatal anatomy, physiology, and surgical management of CHD in the setting of HS. Study Design Retrospective single-center cohort study including all patients with a prenatal diagnosis of HS from 2003 to 2018. Anatomic diagnoses from FE reports were compared with postnatal echocardiogram, catheterization, and operative reports. Prenatal predictions were compared with postnatal outcomes with a focus on ductal dependence, time to first intervention (immediate, neonatal period, 1–6 months, or older than 6 months), and surgical approach (single or biventricular). Results There were 102 pregnancies with fetal HS resulting in 21 terminations, 5 fetal losses, and 76 live births. Of the live births, 55 had significant CHD and available postnatal data for review. Among this group, survival to 1 year was 62% and was no different comparing single versus biventricular surgical approach. FE diagnostic accuracy varied by anatomic feature and was the lowest for diagnosis of venous anatomy. Determination of postnatal care was most accurate for predicting single versus biventricular surgical approach (91%), followed by ductal dependence (75%). Accuracy for predicting time to first intervention was the lowest at 69%. The most common reason for an incorrect prediction was difficulty in assessing the severity of pulmonary stenosis. Conclusion FE permits accurate predictions regarding surgical approach. Characterizing systemic and pulmonary veins is challenging, as is predicting ductal dependence and time to first intervention. These data suggest that despite the high diagnostic accuracy of CHD in HS, a circumspect approach may be reasonable with regard to predicting some anatomic details and postnatal management decisions. Key Points In HS, FE was most accurate for intracardiac anatomy. Diagnostic accuracy of venous anatomy was less reliable. Predicting surgical approach (single ventricle vs. biventricular) was highly accurate. Predicting ductal dependence and time-to-intervention were more challenging in some instances. [ABSTRACT FROM AUTHOR]

BACKGROUND Since the birth of the first baby using IVF technology in 1978, over 10 million children have been conceived via ART. Although most aspects of ARTs were developed in animal models, the introduction of these technologies into clinical practice was performed without comprehensive assessment of their long-term safety. The monitoring of these technologies over time has revealed differences in the physiology of babies produced using ARTs, yet due to the pathology of those presenting for treatment, it is challenging to separate the cause of infertility from the effect of treatments offered. The use of systematic review and meta-analysis to investigate the impacts of the predominant ART interventions used clinically in human populations on animals produced in healthy fertile populations offers an alternative approach to understanding the long-term safety of reproductive technologies. OBJECTIVE AND RATIONALE This systematic review and meta-analysis aimed to examine the evidence available from animal studies on physiological outcomes in the offspring conceived after IVF, IVM or ICSI, compared to in vivo fertilization, and to provide an overview on the landscape of research in this area. SEARCH METHODS PubMed, Embase and Commonwealth Agricultural Bureaux (CAB) Abstracts were searched for relevant studies published until 27 August 2021. Search terms relating to assisted reproductive technology, postnatal outcomes and mammalian animal models were used. Studies that compared postnatal outcomes between in vitro -conceived (IVF, ICSI or IVM) and in vivo -conceived mammalian animal models were included. In vivo conception included mating, artificial insemination, or either of these followed by embryo transfer to a recipient animal with or without in vitro culture. Outcomes included birth weight, gestation length, cardiovascular, metabolic and behavioural characteristics and lifespan. OUTCOMES A total of 61 studies in five different species (bovine, equine, murine, ovine and non-human primate) met the inclusion criteria. The bovine model was the most frequently used in IVM studies (32/40), while the murine model was mostly used in IVF (17/20) and ICSI (6/8) investigations. Despite considerable heterogeneity, these studies suggest that the use of IVF or maturation results in offspring with higher birthweights and a longer length of gestation, with most of this evidence coming from studies in cattle. These techniques may also impair glucose and lipid metabolism in male mice. The findings on cardiovascular outcomes and behaviour outcomes were inconsistent across studies. WIDER IMPLICATIONS Conception via in vitro or in vivo means appears to have an influence on measurable outcomes of offspring physiology, manifesting differently across the species studied. Importantly, it can be noted that these measurable differences are noticeable in healthy, fertile animal populations. Thus, common ART interventions may have long-term consequences for those conceived through these techniques, regardless of the pathology underpinning diagnosed infertility. However, due to heterogeneous methods, results and measured outcomes, highlighted in this review, it is difficult to draw firm conclusions. Optimizing animal and human studies that investigate the safety of new reproductive technologies will provide insight into safeguarding the introduction of novel interventions into the clinical setting. Cautiously prescribing the use of ARTs clinically may also be considered to reduce the chance of promoting adverse outcomes in children conceived before long-term safety is confidently documented. [ABSTRACT FROM AUTHOR]

Background and Objectives: In the last decades, simultaneously increasing trends have been recorded for both caesarean section delivery and childhood overweight/obesity around the world, which are considered serious public health concerns, negatively affecting child health. Aim: The present study aims to investigate whether caesarean section is associated with the increased rates of childhood overweight/obesity, low childbirth anthropometric indices and postnatal complications in pre-school age. Materials and Methods: This is a cross-sectional study in which 5215 pre-school children aged 2–5 years old were enrolled from nine different Greek regions after applying specific inclusion and exclusion criteria. Non-adjusted and adjusted statistical analysis was performed to assess the impact of caesarean section in comparison to vaginal delivery. Results: Children delivered by caesarean section were significantly more frequently overweight or obese at the age of 2–5 years, also presenting a higher prevalence of low birth weight, length and head circumference. Caesarean section was also associated with higher incidence of asthma and diabetes type I at the age of 2–5 years. In a multivariate analysis, caesarean section increased the risk of childhood overweight/obesity and low childbirth anthropometric indices even if adjusting for several childhood and maternal confounding factors. Conclusions: Increasing trends were recorded for both caesarean section delivery and childhood overweight/obesity, which are considered serious public health concerns. Caesarean section independently increased childhood overweight/obesity in pre-school age, highlighting the emergent need to promote health policies and strategies to inform future mothers about its short and long-term risks and that this mode of delivery should preferably be performed only when there are strong medical recommendations in emergency obstetric conditions. [ABSTRACT FROM AUTHOR]

To analyze the normal development of fetal gallbladder (GB) and evaluate the postnatal outcomes of fetuses with isolated GB anomalies without other structural abnormalities by ultrasound. Methods This was a retrospective study. We collected normal cases during 2016 between 15 and 40 gestational weeks and measured the length and width of GB to establish a normal reference range of GB. Using the 10th and 90th percentiles of the normal reference range, isolated cases of enlarged or small GB without other structural anomalies were selected between January 2017 and December 2019. Simultaneously, cases of echogenic material in the GB were included. Fetuses with non-visualization of the fetal gallbladder (NVFGB) were collected between January 2010 and December 2019. Postnatal outcomes of these cases were followed up and analyzed. Results There were 670 cases in the normal group and a linear correlation was found between the dimensions of GB and the gestational age, including the length (r = 0.69; p < .05; y = 0.97 + 0.70 × gestational age) and width (r = 0.48; p < .05; y = 1.65 + 0.12 × gestational age). Sixty-two cases with isolated GB anomalies were collected, including nine cases of enlarged GB, four cases of small GB, three cases of echogenic material in the GB, and 46 cases of NVFGB. Sixty fetuses (96.8%, 60/62) had good outcomes, except that two neonates (4%, 2/50) in small GB and NVFGB groups were both born with BA. In the NVFGB group, 97.8% (45/46) were with good outcomes, in which gallbladders were finally visualized in 37 (80.4%, 37/46) cases and GB agenesis was postnatally diagnosed in eight (17.4%, 8/46) patients by ultrasound. Conclusion The postnatal outcomes of most fetuses (96.8%) with isolated GB anomalies such as enlarged GB, echogenic material in the GB were favorable. When it comes to cases of small GB or NVFGB in prenatal ultrasound diagnosis, we should alert biliary atresia in prenatal counseling. [ABSTRACT FROM AUTHOR]

Abstract Background The implementation of genomic testing in pregnancy means that couples have access to more information about their child’s genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years. Methods This study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old’s), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed. Discussion This study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy. Trial registration ACTRN12620000446965p ; Registered on April 6, 2020.

BackgroundAberrant right subclavian artery (ARSA) is becoming increasingly common in fetuses. However, there are relatively fewer studies regarding the genetic etiology of ARSA. We performed a genetic analysis of fetuses with ARSA and followed up on the pregnancy outcomes to evaluate the prognosis of the fetuses, providing information for prenatal and eugenic consultations.MethodsThis retrospective study included 112 pregnant females whose fetuses were diagnosed with ARSA from December 2016 to February 2021. Fetal karyotype analysis and single-nucleotide polymorphism (SNP) array were performed.ResultsThe 112 fetuses were divided into two groups: the isolated ARSA group (n = 48, 42.9%) and the non-isolated ARSA group (ARSA with other ultrasound abnormalities, n = 64, 57.1%). The total rate of pathogenic copy number variation (CNV) observed using karyotype analysis (3/8) and SNP array (5/8) was 7.1% (8/112). The rates of pathogenic CNV in the isolated and non-isolated ARSA groups were 4.2% (2/48) and 9.4% (6/64), respectively. No significant difference was observed between the two groups (P = 0.463). The results of genetic analysis influenced the parents’ decision to terminate the pregnancy. During the follow-up examination, fetuses with ARSA without pathogenic CNV were found to have normal growth and development after birth.ConclusionFetuses with isolated ARSA have a low probability of being diagnosed with pathogenic CNV. However, when ARSA is complicated with other ultrasound abnormalities, the risk of pathogenic CNV remarkably increases. Prenatal genetic counseling and SNP-array should be recommended for better assessment of fetal prognosis.

Background and Objectives: In the last decades, simultaneously increasing trends have been recorded for both caesarean section delivery and childhood overweight/obesity around the world, which are considered serious public health concerns, negatively affecting child health. Aim: The present study aims to investigate whether caesarean section is associated with the increased rates of childhood overweight/obesity, low childbirth anthropometric indices and postnatal complications in pre-school age. Materials and Methods: This is a cross-sectional study in which 5215 pre-school children aged 2–5 years old were enrolled from nine different Greek regions after applying specific inclusion and exclusion criteria. Non-adjusted and adjusted statistical analysis was performed to assess the impact of caesarean section in comparison to vaginal delivery. Results: Children delivered by caesarean section were significantly more frequently overweight or obese at the age of 2–5 years, also presenting a higher prevalence of low birth weight, length and head circumference. Caesarean section was also associated with higher incidence of asthma and diabetes type I at the age of 2–5 years. In a multivariate analysis, caesarean section increased the risk of childhood overweight/obesity and low childbirth anthropometric indices even if adjusting for several childhood and maternal confounding factors. Conclusions: Increasing trends were recorded for both caesarean section delivery and childhood overweight/obesity, which are considered serious public health concerns. Caesarean section independently increased childhood overweight/obesity in pre-school age, highlighting the emergent need to promote health policies and strategies to inform future mothers about its short and long-term risks and that this mode of delivery should preferably be performed only when there are strong medical recommendations in emergency obstetric conditions.

Intracranial hemorrhage (ICH) in pregnancy, estimated at 1 in 10,000 cases, presents significant diagnostic challenges prenatally despite advanced imaging techniques such as ultrasonography (US) and magnetic resonance imaging (MRI). Detecting ICH is crucial for pregnancy management and future treatment decisions aimed at improving fetal survival and reducing brain damage. This report presents the diagnosis and outcomes of 2 cases of prenatal ICH. The first case involves a 30-year-old pregnant woman with irregular prenatal care diagnosed with ICH at 32 weeks of gestation via US and MRI. She chose to continue the pregnancy, delivering a 3160 g male infant at 36 weeks via cesarean section. Following NICU care including resuscitation and ventriculoperitoneal shunt placement, the infant was discharged. Subsequent examinations showed a reduction in ventricle size. In the second case, a 27-year-old woman taking acenocoumarol for a mechanical heart valve developed fetal subdural hemorrhage detected by US and MRI. She opted to terminate the pregnancy, resulting in a stillborn male infant weighing 1530 g. Fetal ICH presents with varying severity and prognostic implications, diagnosed and graded using US. Fetal cranial MRI may help clarify the etiology. Management remains controversial, with termination of pregnancy potentially warranted in severe cases due to poor prognosis. Further research is needed to refine management and improve outcomes in fetal ICH., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: The implementation of genomic testing in pregnancy means that couples have access to more information about their child's genetic make-up before birth than ever before. One of the resulting challenges is the management of genetic variations with unclear clinical significance. This population-based study will help to close this critical knowledge gap through a multidisciplinary cohort study of children with and without genomic copy number variants (CNVs) diagnosed before birth. By comparing children with prenatally-ascertained CNVs to children without a CNV, we aim to (1) examine their developmental, social-emotional and health status; (2) measure the impact of prenatal diagnosis of a CNV on maternal perceptions of child health, behavior and development; and (3) determine the proportion of prenatally-ascertained CNVs of unknown or uncertain significance that are reclassified as benign or pathogenic after 2 or more years. Methods: This study will establish and follow up a cohort of mother-child pairs who have had a prenatal diagnosis with a chromosomal microarray from 2013-2019 in the Australian state of Victoria. Children aged 12 months to 7 years will be assessed using validated, age-appropriate measures. The primary outcome measures will be the Wechsler Preschool and Primary Scale of Intelligence IV (WPSSI-IV) IQ score (2.5 to 7 year old's), the Ages and Stages Questionnaire (12-30 months old), and the Brief Infant- Toddler Social and Emotional Assessment (BITSEA) score. Clinical assessment by a pediatrician will also be performed. Secondary outcomes will be scores obtained from the: Vineland Adaptive Behavior Scale, Maternal Postnatal Attachment Questionnaire, the Vulnerable Child Scale, Profile of Mood States, Parent Sense of Competence Scale. A descriptive analysis of the reclassification rates of CNVs after ≥2 years will be performed. Discussion: This study protocol describes the first Australian cohort study following children after prenatal diagnostic testing with chromosomal microarray. It will provide long-term outcomes of fetal genomic variants to guide evidence-based pre-and postnatal care. This, in turn, will inform future efforts to mitigate the negative consequences of conveying genomic uncertainty during pregnancy. Trial registration: ACTRN12620000446965p; Registered on April 6, 2020. [ABSTRACT FROM AUTHOR]

Objective: To review the perinatal and long-term outcomes of symmetric and ventrally conjoined twins evaluated prenatally by ultrasound and fetal magnetic resonance imaging (MRI).Methods: From March 2010 to January 2019, cases of symmetric and ventrally conjoined twins, who were prenatally diagnosed and referred to the Clínica Diagnóstico por Imagem (CDPI), Rio de Janeiro, Brazil, for prenatal evaluation by ultrasound and MRI were selected. The postnatal information was collected from hospitals where the twins were born and/or treated and from parents' verbal and written information.Results: Four cases of symmetrical and ventrally conjoined twins were selected. Of these, two were omphalopagi and two thoracopagi. One pair of thoracomphalopagus died early in utero and the other died 6 days after birth. The outcome of the two omphalopagus pairs were separation in emergency surgeries after birth, with neonatal demise of one of the twins due to congenital malformations. In cases of omphalopagi, fetal MRI presented important information of the twins' anatomy before emergency separation of both pairs.Conclusion: Despite the apparently similar conditions of twins with ventral fusion, ventrally attached twins have very different outcomes, most adverse for thoracomphalopagus and related to the singular anatomy of the pair, associated malformations and the extension of the adhesion, requiring individual evaluation of the cases. Fetal MRI is as an important tool for the postnatal surgery management of twin neonates, providing crucial information in cases where urgent separation is required. [ABSTRACT FROM AUTHOR]

Nowadays, assisted reproductive technologies (ARTs) are considered valuable contributors to our past, but a future without their use is inconceivable. However, in recent years, several studies have evidenced a potential impact of ART on long-term development in mammal species. To date, the long-term follow-up data are still limited. So far, studies have mainly focused on in vitro fertilization or in vitro culture, with information from gametes/embryos cryopreservation field being practically missing. Herein, we report an approach to determine whether a vitrified embryo transfer procedure would have long-term consequences on the offspring. Using the rabbit as a model, we compared animals derived from vitrified-transferred embryos versus those naturally conceived, studying the growth performance, plus the weight throughout life, and the internal organs/tissues phenotype. The healthy status was assessed over the hematological and biochemical parameters in peripheral blood. Additionally, a comparative proteomic analysis was conducted in the liver tissue to investigate molecular cues related to vitrified embryo transfer in an adult tissue. After vitrified embryo transfer, birth weight was increased, and the growth performance was diminished in a sex-specific manner. In addition, vitrified-transferred animals showed significantly lower body, liver and heart weights in adulthood. Molecular analyses revealed that vitrified embryo transfer triggers reprogramming of the liver proteome. Functional analysis of the differentially expressed proteins showed changes in relation to oxidative phosphorylation and dysregulations in the zinc and lipid metabolism, which has been reported as possible causes of a disturbed growth pattern. Therefore, we conclude that vitrified embryo transfer is not a neutral procedure, and it incurs long-term effects in the offspring both at phenotypic and molecular levels. These results described a striking example of the developmental plasticity exhibited by the mammalian embryo.

In this study, we evaluated the effect of embryo vitrification using two different devices on adulthood phenotype in rabbits. In vitro development, prenatal embryo survival, body weight, growth performance, haematological and biochemical peripheral blood analysis, reproductive performance, and lactation performance traits were compared between the experimental groups. They derived from naturally-conceived embryos (NC), fresh-transferred embryos (FT), vitrified-transferred embryos using mini-straw (VTs), or vitrified-transferred embryos using Cryotop (VTc). Straw-vitrified embryos exhibited lower in vitro developmental rates and in vivo survival rates following embryo transfer compared to its Cryotop-vitrified counterparts. Moreover, the VTs group exhibited higher foetal losses than VTc, FT, and NC groups. Independently of the vitrification device, vitrified-transferred (VT) offspring showed a skewed sex ratio in favour of males, and an increased birth bodyweight. In contrast, postnatal daily growth was diminished in all ART (i.e., FT and VT) animals. In adulthood, significant differences in body weight between all groups was founded—all ART progenies weighed less than NC animals and, within ART, VT animals weighed less than FT. For VT groups, weight at adulthood was higher for the VTs group compared with the VTc group. Peripheral blood parameters ranged between common values. Moreover, no differences were found in the fertility rates between experimental groups. Furthermore, similar pregnancy rates, litter sizes, and the number of liveborns were observed, regardless of the experimental group. However, decreased milk yield occurred for VTc and FT animals compared to VTs and NC animals. A similar trend was observed for the milk composition of dry matter and fat. Concordantly, reduced body weight was found for suckling kits in the VTc and FT groups compared to VTs and NC animals. Our findings reveal that developmental changes after the embryo vitrification procedure could be associated with an exhibition of the embryonic developmental plasticity. Moreover, to our best knowledge, this study reports the first evidence demonstrating that the vitrification device used is not a trivial decision, providing valuable information about how the cooling–warming rates during vitrification can be partly responsible of the postnatal phenotypic variations.

Fetal growth is regulated by a complex interaction of maternal, placental, and fetal factors. The effects and outcomes that chemicals, widely distributed in the environment, may have on the health status of both the mother and the fetus are not yet well defined. Mainly mixtures of chemical substances are found in the mothers and placenta. Exposure to endocrine-disrupting chemicals (EDCs) can be associated with fetal growth retardation, thyroid dysfunction, and neurological disorders. EDCs mostly interfere with insulin, glucocorticoid, estrogenic, and thyroid pathways, with subsequent effects on normal endocrine and metabolic functions, which cause changes in the epigenome and state of inflammation with life-long effects and consequences. International scientific societies recommend the implementation of research and of all possible preventive measures. This review briefly summarizes all these aspects.

Male and female infants respond differentially to environmental stimuli, with different growth and neurodevelopmental trajectories. Male infants are more likely to be disadvantaged when subjected to adversity and show a higher risk of perinatal complications. However, the underlying causes of this sex-bias are not well defined and optimising the early life nutritional care may be necessary to minimise the “male disadvantage” that may be experienced early in life. Experimental models have demonstrated that animal milk composition differs according to offspring sex, suggesting that the tailoring of early life nutrition may be one mechanism to maximise health protection and development to infants of both sexes. However, evidence for a sex-specificity in human milk composition is limited and conflicting, with studies documenting higher milk energy content for either male or female infants. These data show sex differences, however, there has been limited compositional analysis of the current data nor strategies proposed for how sex-specific compositional differences in early life nutrition may be used to improve infant health. The present narrative review highlights that an improved understanding of sex-specific human milk composition is essential for promoting optimal infant growth and development.

The study examined the association between pregnancy intention among young Filipino women and prenatal, delivery and postnatal outcomes. Data were drawn from the 2013 Young Adult Fertility and Sexuality Study, a nationally representative survey of 19,178 Filipino youth aged between 15 and 24. The analytic sample consists of 2,264 live births in the two years prior to the survey. The survey shows that 38.7 per cent of births were unintended at the time of conception: 23.1 per cent were mistimed while 15.6 per cent were unwanted. Proportionately, more unintended births were borne by mothers who were teenagers, unmarried, college-educated, urban and Metro Manila residents than their counterparts. There were also more unintended births among first-order births than among subsequent births. Logistic regression results show that compared with mothers of intended births, mothers of mistimed and unwanted births were more likely to have attempted to abort their pregnancy. Mothers of mistimed births are also less likely to have begun prenatal care within the first trimester of pregnancy than mothers of intended births. The findings suggest that unintended pregnancy is an important consideration in interventions aimed at improving maternal and child health but further studies are needed to fully explore the dynamics between unintended pregnancy and maternal health outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the normal development of fetal gallbladder (GB) and evaluate the postnatal outcomes of fetuses with isolated GB anomalies without other structural abnormalities by ultrasound., Methods: This was a retrospective study. We collected normal cases during 2016 between 15 and 40 gestational weeks and measured the length and width of GB to establish a normal reference range of GB. Using the 10th and 90th percentiles of the normal reference range, isolated cases of enlarged or small GB without other structural anomalies were selected between January 2017 and December 2019. Simultaneously, cases of echogenic material in the GB were included. Fetuses with non-visualization of the fetal gallbladder (NVFGB) were collected between January 2010 and December 2019. Postnatal outcomes of these cases were followed up and analyzed., Results: There were 670 cases in the normal group and a linear correlation was found between the dimensions of GB and the gestational age, including the length ( r  = 0.69; p  < .05; y  = 0.97 + 0.70 × gestational age) and width ( r  = 0.48; p  < .05; y  = 1.65 + 0.12 × gestational age). Sixty-two cases with isolated GB anomalies were collected, including nine cases of enlarged GB, four cases of small GB, three cases of echogenic material in the GB, and 46 cases of NVFGB. Sixty fetuses (96.8%, 60/62) had good outcomes, except that two neonates (4%, 2/50) in small GB and NVFGB groups were both born with BA. In the NVFGB group, 97.8% (45/46) were with good outcomes, in which gallbladders were finally visualized in 37 (80.4%, 37/46) cases and GB agenesis was postnatally diagnosed in eight (17.4%, 8/46) patients by ultrasound., Conclusion: The postnatal outcomes of most fetuses (96.8%) with isolated GB anomalies such as enlarged GB, echogenic material in the GB were favorable. When it comes to cases of small GB or NVFGB in prenatal ultrasound diagnosis, we should alert biliary atresia in prenatal counseling.

Background: Aberrant right subclavian artery (ARSA) is becoming increasingly common in fetuses. However, there are relatively fewer studies regarding the genetic etiology of ARSA. We performed a genetic analysis of fetuses with ARSA and followed up on the pregnancy outcomes to evaluate the prognosis of the fetuses, providing information for prenatal and eugenic consultations., Methods: This retrospective study included 112 pregnant females whose fetuses were diagnosed with ARSA from December 2016 to February 2021. Fetal karyotype analysis and single-nucleotide polymorphism (SNP) array were performed., Results: The 112 fetuses were divided into two groups: the isolated ARSA group ( n = 48, 42.9%) and the non-isolated ARSA group (ARSA with other ultrasound abnormalities, n = 64, 57.1%). The total rate of pathogenic copy number variation (CNV) observed using karyotype analysis (3/8) and SNP array (5/8) was 7.1% (8/112). The rates of pathogenic CNV in the isolated and non-isolated ARSA groups were 4.2% (2/48) and 9.4% (6/64), respectively. No significant difference was observed between the two groups ( P = 0.463). The results of genetic analysis influenced the parents' decision to terminate the pregnancy. During the follow-up examination, fetuses with ARSA without pathogenic CNV were found to have normal growth and development after birth., Conclusion: Fetuses with isolated ARSA have a low probability of being diagnosed with pathogenic CNV. However, when ARSA is complicated with other ultrasound abnormalities, the risk of pathogenic CNV remarkably increases. Prenatal genetic counseling and SNP-array should be recommended for better assessment of fetal prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cai, Lin, Fan, Chen, Xu, Fu, Xu and Huang.)

Early postpartum home visiting is universal in many Western countries. Studies from developing countries on the effects of home visits are rare. In Syria, where the postpartum period is rather ignored, this study aimed to assess whether a community-based intervention of postnatal home visits has an effect on maternal postpartum morbidities; infant morbidity; uptake of postpartum care; use of contraceptive methods; and on selected neonatal health practices. Design: A randomized controlled trial was carried out in Damascus. Three groups of new mothers were randomly allocated to receive either 4 postnatal home visits (A), one visit (B), or no visit (C). Sample: A total of 876 women were allocated and followed up. Intervention: Registered midwives with special training made a one or a series of home visits providing information, educating, and supporting women. Results: A significantly higher proportion of mothers in Groups A and B reported exclusively breastfeeding their infants (28.5% and 30%, respectively) as compared with Group C (20%), who received no visits. There were no reported differences between groups in other outcomes. Conclusions: While postpartum home visits significantly increased exclusive breastfeeding, other outcomes did not change. Further studies framed in a nonbiomedical context are needed. Other innovative approaches to improve postnatal care in Syria are needed. [ABSTRACT FROM AUTHOR]

SUMMARY 1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm birth following intra-uterine growth restriction (IUGR) are unknown. Thus, our objectives were: (i) to identify prenatal factors associated with preterm birth in IUGR fetuses; and (ii) to characterize postnatal effects of preterm birth following IUGR. 2. We studied pregnant sheep and their offspring, in which fetal growth was restricted by umbilico-placental embolization during late gestation. Some of these animals were born at term (146±1 days) and some were born prematurely (139±1 days). In both groups, we have conducted longitudinal studies of postnatal respiratory function, cardiovascular function and learning ability up to 6-8 weeks of age. 3. Before birth, IUGR fetuses born prematurely (P-IUGR) were more hypoxaemic and acidaemic and had higher haemoglobin concentrations than both control fetuses and IUGR fetuses born at term (T-IUGR). In P-IUGR fetuses, plasma cortisol concentrations increased earlier than in the two other groups. The P-IUGR lambs had lower birthweights than T-IUGR lambs and both groups of IUGR lambs remained lighter than controls for 8 weeks. 4. After birth, P-IUGR lambs were hypoxaemic compared with T-IUGR and control lambs. Pulmonary diffusing capacity (adjusted for lung volume) was significantly lower in both groups of IUGR lambs than in controls, with P-IUGR lambs having lower values than T-IUGR lambs. Lung compliance (adjusted for lung volume), was not different between P-IUGR and control lambs, but values were higher in T-IUGR lambs than in control and P-IUGR lambs. Chest wall compliance (adjusted for lung volume) was higher in both groups of IUGR lambs than in controls. 5. During the 8 week postnatal... [ABSTRACT FROM AUTHOR]

Simple Summary: This study was conducted to demonstrate how a vitrified embryo transfer procedure incurs phenotypic and molecular changes throughout life. This study reports the first evidence describing that embryonic manipulation during a vitrified embryo transfer cycle induced molecular modifications, concerning oxidative phosphorylation and dysregulations in zinc and lipid metabolism in liver tissue, which has been reported as responsible for postnatal variations of the phenotype. Nowadays, assisted reproductive technologies (ARTs) are considered valuable contributors to our past, but a future without their use is inconceivable. However, in recent years, several studies have evidenced a potential impact of ART on long-term development in mammal species. To date, the long-term follow-up data are still limited. So far, studies have mainly focused on in vitro fertilization or in vitro culture, with information from gametes/embryos cryopreservation field being practically missing. Herein, we report an approach to determine whether a vitrified embryo transfer procedure would have long-term consequences on the offspring. Using the rabbit as a model, we compared animals derived from vitrified-transferred embryos versus those naturally conceived, studying the growth performance, plus the weight throughout life, and the internal organs/tissues phenotype. The healthy status was assessed over the hematological and biochemical parameters in peripheral blood. Additionally, a comparative proteomic analysis was conducted in the liver tissue to investigate molecular cues related to vitrified embryo transfer in an adult tissue. After vitrified embryo transfer, birth weight was increased, and the growth performance was diminished in a sex-specific manner. In addition, vitrified-transferred animals showed significantly lower body, liver and heart weights in adulthood. Molecular analyses revealed that vitrified embryo transfer triggers reprogramming of the liver proteome. Functional analysis of the differentially expressed proteins showed changes in relation to oxidative phosphorylation and dysregulations in the zinc and lipid metabolism, which has been reported as possible causes of a disturbed growth pattern. Therefore, we conclude that vitrified embryo transfer is not a neutral procedure, and it incurs long-term effects in the offspring both at phenotypic and molecular levels. These results described a striking example of the developmental plasticity exhibited by the mammalian embryo. [ABSTRACT FROM AUTHOR]

Simple Summary: This study was conducted to demonstrate how embryo manipulation techniques incur phenotypic changes throughout life. This study reports the first evidence demonstrating that the vitrification device used is not a trivial decision, providing valuable information about how the cooling–warming rates during vitrification can be partly responsible of the postnatal phenotypic variations. In this study, we evaluated the effect of embryo vitrification using two different devices on adulthood phenotype in rabbits. In vitro development, prenatal embryo survival, body weight, growth performance, haematological and biochemical peripheral blood analysis, reproductive performance, and lactation performance traits were compared between the experimental groups. They derived from naturally-conceived embryos (NC), fresh-transferred embryos (FT), vitrified-transferred embryos using mini-straw (VTs), or vitrified-transferred embryos using Cryotop (VTc). Straw-vitrified embryos exhibited lower in vitro developmental rates and in vivo survival rates following embryo transfer compared to its Cryotop-vitrified counterparts. Moreover, the VTs group exhibited higher foetal losses than VTc, FT, and NC groups. Independently of the vitrification device, vitrified-transferred (VT) offspring showed a skewed sex ratio in favour of males, and an increased birth bodyweight. In contrast, postnatal daily growth was diminished in all ART (i.e., FT and VT) animals. In adulthood, significant differences in body weight between all groups was founded—all ART progenies weighed less than NC animals and, within ART, VT animals weighed less than FT. For VT groups, weight at adulthood was higher for the VTs group compared with the VTc group. Peripheral blood parameters ranged between common values. Moreover, no differences were found in the fertility rates between experimental groups. Furthermore, similar pregnancy rates, litter sizes, and the number of liveborns were observed, regardless of the experimental group. However, decreased milk yield occurred for VTc and FT animals compared to VTs and NC animals. A similar trend was observed for the milk composition of dry matter and fat. Concordantly, reduced body weight was found for suckling kits in the VTc and FT groups compared to VTs and NC animals. Our findings reveal that developmental changes after the embryo vitrification procedure could be associated with an exhibition of the embryonic developmental plasticity. Moreover, to our best knowledge, this study reports the first evidence demonstrating that the vitrification device used is not a trivial decision, providing valuable information about how the cooling–warming rates during vitrification can be partly responsible of the postnatal phenotypic variations. [ABSTRACT FROM AUTHOR]

Fetal growth is regulated by a complex interaction of maternal, placental, and fetal factors. The effects and outcomes that chemicals, widely distributed in the environment, may have on the health status of both the mother and the fetus are not yet well defined. Mainly mixtures of chemical substances are found in the mothers and placenta. Exposure to endocrine-disrupting chemicals (EDCs) can be associated with fetal growth retardation, thyroid dysfunction, and neurological disorders. EDCs mostly interfere with insulin, glucocorticoid, estrogenic, and thyroid pathways, with subsequent effects on normal endocrine and metabolic functions, which cause changes in the epigenome and state of inflammation with life-long effects and consequences. International scientific societies recommend the implementation of research and of all possible preventive measures. This review briefly summarizes all these aspects. [ABSTRACT FROM AUTHOR]

Male and female infants respond differentially to environmental stimuli, with different growth and neurodevelopmental trajectories. Male infants are more likely to be disadvantaged when subjected to adversity and show a higher risk of perinatal complications. However, the underlying causes of this sex-bias are not well defined and optimising the early life nutritional care may be necessary to minimise the "male disadvantage" that may be experienced early in life. Experimental models have demonstrated that animal milk composition differs according to offspring sex, suggesting that the tailoring of early life nutrition may be one mechanism to maximise health protection and development to infants of both sexes. However, evidence for a sex-specificity in human milk composition is limited and conflicting, with studies documenting higher milk energy content for either male or female infants. These data show sex differences, however, there has been limited compositional analysis of the current data nor strategies proposed for how sex-specific compositional differences in early life nutrition may be used to improve infant health. The present narrative review highlights that an improved understanding of sex-specific human milk composition is essential for promoting optimal infant growth and development. [ABSTRACT FROM AUTHOR]