Early Growth Delay Research Articles

Embryonic, Fetal, and Neonatal Complications in Infants of Diabetic Mothers: Insights from the Cincinnati Diabetes in Pregnancy Program Project Grant.

This study aimed to review how the Cincinnati Diabetes in Pregnancy Program Project Grant (PPG) contributed to the understanding and treatment of neonatal complications in infants of diabetic mothers (IDMs). This is a retrospective review of all PPG work on glycemic control at different pregnancy time points and its association with embryonic, fetal, and neonatal complications, such as congenital malformations (CMs), intrauterine growth restriction, macrosomia, hypoglycemia, respiratory distress syndrome (RDS), asphyxia, and polycythemia. We found that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal hypoglycemic episodes or insulin therapy, are independent risk factors for major CMs. A suggestive association of major CMs with maternal Magnesium deficiency was also observed. Poor glycemic control during late embryogenesis and early fetal development was associated with an increased risk of minor CMs. We described a biphasic pattern of fetal growth whereby early growth delay was followed by enhanced fetal growth associated with neonatal macrosomia. Macrosomia was associated with poorer glycemic control in the third trimester and an increased risk of birth trauma. Macrosomia was also correlated with animal-origin insulin concentrations in cord blood, demonstrating that insulin bound to antibodies can cross the placenta and may affect the fetus. We also showed that neonatal hypoglycemia was significantly associated with third-trimester glycemic control, in addition to hyperglycemia occurring during labor. With modern management and adequate prenatal care, IDMs are no longer at increased risk for RDS. Perinatal asphyxia was associated with increased proteinuria appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. Polycythemia in IDMs is prevalent and correlates with proxy measurements of fetal hypoxemia (nucleated red blood cells at delivery) and poorer glycemic control in late pregnancy. The PPG in its various phases revealed the important role of glycemic control at nearly every stage of pregnancy including labor. KEY POINTS: · Poor glycemic control during embryogenesis is a major risk factor for CMs.. · Magnesium deficiency might contribute to major malformations.. · Macrosomia is associated with poor glycemic control in the third trimester.. · Strict glycemic control reduces fetal and neonatal morbidity in pregnancies with insulin-dependent diabetes mellitus..

An in-vivo study of the combined therapeutic effects of pulsed non-thermal focused ultrasound and radiation for prostate cancer

Purpose The purpose of this study was to investigate the in vivo combined effects of pulsed focused ultrasound (pFUS) and radiation (RT) for prostate cancer treatment. Materials and Methods An animal prostate tumor model was developed by implanting human LNCaP tumor cells in the prostates of nude mice. Tumor-bearing mice were treated with pFUS, RT or both (pFUS + RT) and compared with a control group. Non-thermal pFUS treatment was delivered by keeping the body temperature below 42 °C as measured real-time by MR thermometry and using a pFUS protocol (1 MHz, 25 W focused ultrasound; 1 Hz pulse rate with a 10% duty cycle for 60 sec for each sonication). Each tumor was covered entirely using 4–8 sonication spots. RT treatment with a dose of 2 Gy was delivered using an external beam (6 MV photon energy with dose rate 300MU/min). Following the treatment, mice were scanned weekly with MRI for tumor volume measurement. Results The results showed that the tumor volume in the control group increased exponentially to 142 ± 6%, 205 ± 12%, 286 ± 22% and 410 ± 33% at 1, 2, 3 and 4 weeks after treatment, respectively. In contrast, the pFUS group was 29% (p < 0.05), 24% (p < 0.05), 8% and 9% smaller, the RT group was 7%, 10%, 12% and 18% smaller, and the pFUS + RT group was 32%, 39%, 41% and 44% (all with p < 0.05) smaller than the control group at 1, 2, 3, and 4 weeks post treatment, respectively. Tumors treated by pFUS showed an early response (i.e. the first 2 weeks), while the RT group showed a late response. The combined pFUS + RT treatment showed consistent response throughout the post-treatment weeks. Conclusions These results suggest that RT combined with non-thermal pFUS can significantly delay the tumor growth. The mechanism of tumor cell killing between pFUS and RT may be different. Pulsed FUS shows early tumor growth delay, while RT contributes to the late effect on tumor growth delay. The addition of pFUS to RT significantly enhanced the therapeutic effect for prostate cancer treatment.

Spinocerebellar ataxia 21 and phenotypic variability within a single family (P9-11.004)

<h3>Objective:</h3> We describe four patients within a family who presented to our movement disorders centers for evaluation of unsteady gait, tremor, and cognitive impairment found to have the same pathogenic variant in TMEM240. We describe their clinical courses and response to treatments to include posterior subthalamic area deep brain stimulation (PSA DBS) and provide accompanying video. <h3>Background:</h3> Spinocerebellar ataxia 21 (SCA21) is a rare cause of autosomal dominant ataxia with few patients (~50) published. It is an early-onset, slowly progressive cerebellar ataxia and may also have tremor, parkinsonism, oculomotor abnormalities, cognitive impairment, and psychiatric conditions. Given its rarity, the neurodevelopmental phenotype has not been well defined and phenotypic variability within the same variant has not yet described. <h3>Design/Methods:</h3> The index case, 12 year-old girl, presented with mild intellectual disability, severe action tremor since infancy, oculomotor abnormalities, anxiety, and depression. The full brother was noted to have mild action tremor since early childhood, speech delay and growth delay. The paternal half-brother presented with progressively worsening action tremor since early childhood which became impairing in adolescence as well as similar oculomotor abnormalities, learning disabilities, ADHD, and OCD. The father of the patients had onset of mild non-progressive action tremor of the hands since age 8, progressive ataxia, mild parkinsonism, mild intellectual disability and new onset progressive memory impairment. All patients were found to have the same pathogenic variant in TMEM240 (c.196G&gt;A p.G66R)). <h3>Results:</h3> The index patient tried numerous oral medications as well as botulinum neurotoxin (BoNT) injections without improvement. She underwent PSA DBS with marked improvement in tremor. Tremor in the paternal half-brother responded well to BoNT injections. The father underwent treatment for parkinsonism with carbidopa-levodopa and was started on rivastigmine without improvement. <h3>Conclusions:</h3> SCA21 is a slowly progressive autosomal dominant spinocerebellar ataxia with variable neurodevelopmental phenotypes including multiple movement disorders within the same variant. <b>Disclosure:</b> Dr. Hull has received publishing royalties from a publication relating to health care. Dr. Parnes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Pharmaceuticals. Dr. Parnes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Pharmaceuticals. The institution of Dr. Parnes has received research support from NIH. The institution of Dr. Parnes has received research support from Alexion. Dr. Jankovic has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Revance. Dr. Jankovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Revance, Allergan. The institution of Dr. Jankovic has received research support from Baylor College of Medicine. Dr. Jankovic has received research support from Abbvie. The institution of Dr. Jankovic has received research support from Abbvie.

Natural history of growth and anaemia in children with epidermolysis bullosa: a retrospective cohort study.

Impaired growth and anaemia are major extracutaneous complications of epidermolysis bullosa (EB), but data on their development are lacking. To determine the clinical course of growth and anaemia in children with EB and clarify the impact of nutritional compromise, inflammation and genetic factors. A retrospective study was conducted of 200 children, 157 with recessive dystrophic EB (RDEB) and 43 with junctional EB (JEB)-generalized intermediate, followed at the main referral centre in Germany. Growth charts were calculated using the modified LMS method and were correlated with parameters of anaemia, nutrition, inflammation and the molecular defect in a linear model. In our cohort of patients with RDEB, weight impairment started at 12-18 months old; by the age of 10 years, 50% showed wasting. The predicted median weight at age 20 years was 35·2 kg for men and 40·1 kg for women. In JEB, growth resembled that of healthy children. Anaemia was present from the second year of life onwards in RDEB and JEB. Low levels of haemoglobin, iron, vitamin D, zinc and albumin, high levels of C-reactive protein, and absence of collagen VII correlated significantly with low weight in RDEB. No correlation was observed in JEB. The results highlight that nutritional compromise occurs early in children with RDEB and therefore may require interventions as of the first year or two of life. What's already known about this topic? Children with epidermolysis bullosa (EB) suffer from failure to thrive and anaemia as major extracutaneous complications. The course of growth and the development of anaemia in EB are poorly characterized. What does this study add? A molecularly well characterized cohort of 200 children with EB was followed with regard to anthropometrics, anaemia and inflammation. We demonstrate early onset of growth failure and anaemia, most pronounced in the subset of recessive dystrophic EB. Awareness of early growth delay and nutritional deficiencies will improve EB care in daily practice.

UVC-Emitting LuPO4:Pr3+ Nanoparticles Decrease Radiation Resistance of Hypoxic Cancer Cells.

Radiation-resistant hypoxic tumor areas continue to present a major limitation for successful tumor treatment. To overcome this radiation resistance, an oxygen-independent treatment is proposed using UVC-emitting LuPO4:Pr3+ nanoparticles (NPs) and X rays. The uptake of the NPs as well as their effect on cell proliferation was investigated on A549 lung cancer cells by using inverted time-lapse microscopy and transmission electron microscopy. Furthermore, cytotoxicity of the combined treatment of X rays and LuPO4:Pr3+ NPs was assessed under normoxic and hypoxic conditions using the colony formation assay. Transmission electron microscopy (TEM) images showed no NP uptake after 3 h, whereas after 24 h incubation an uptake of NPs was documented. LuPO4:Pr3+ NPs alone caused a concentration-independent cell growth delay within the first 60 h of incubation. The combined treatment with UVC-emitting NPs and X rays reduced the radiation resistance of hypoxic cells by a factor of two to the level of cells under normoxic condition. LuPO4:Pr3+ NPs cause an early growth delay but no cytotoxicity for the tested concentration. The combination of these NPs with X rays increases cytotoxicity of normoxic and hypoxic cancer cells. Hypoxic cells become sensitized to normoxic cell levels.

A study to analyze the correlation between nutritional dermatoses with socioeconomic status, dietary fallacies and growth in children 1 to 5 years of age, in and around rural area

Background: Little information is available about the prevalence of skin conditions among the children in general population. Skin conditions vary in frequencies and severity in different age groups, different geographical locations and under different definitions of skin diseases. Low socioeconomic status, malnutrition, overcrowding, poor standards of hygiene are important factors accounting for development of nutritional dermatoses in developing countries such as India. The objective of the present research was to study the association between nutritional dermatoses with Socioeconomic status, dietary fallacies and growth in children 1 to 5 years of age. Methods: A cross sectional study was conducted in a rural based medical college of Dakshina Kannada District in Karnataka among the one to five years age children, who were attending the Pediatric out patient with nutritional skin lesions from the month of November 2012 to October 2013. The sample size was estimated as 150 children.Results: In present study, 76.00% (114) of children fall in the group of under nutrition and 73.33% (110) children is having the causative factor as Dietary Fallacies. Majority of children 60.66% (91) with nutritional dermatoses belongs to class IV socio-economic status according to B.G Prasad classification, 27.33% (41) belongs to class III and 12.00% (18) children belongs to class V. 64.66% (97) of children with nutritional dermatoses were underweight, 47.33% (71) of children showed wasting and 35.30% (53) children were stunted.Conclusions: Lower socioeconomic condition and dietary fallacies were the two most causative factors which had an adverse effect on nutritional status of child causing dermatoses. Nutrition deficiency had an impact of early transitional growth failure and delay in the achieving mile stone.

Short-term and long-term sequelae in intrauterine growth retardation (IUGR)

Intrauterine Growth Retardation (IUGR) is defined as a rate of growth of a fetus that is less than normal for the growth potential of the fetus (for that particular gestational age). Small for Gestational Age (SGA) is defined infant born following IUGR, with a weight at birth below the 10th percentile.Suboptimal fetal growth occurring in IUGR fetuses is an important cause of perinatal mortality and morbidity. The acute neonatal consequences of IUGR include metabolic and hematological disturbances, and disrupted thermoregulation; in addition, respiratory distress (RDS), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP) may contribute to perinatal morbidity. Metabolic disturbances are related to glucose and fatty acid metabolism. It is well-known that individuals who display poor growth in utero are at significantly increased risk for type 2 diabetes mellitus (T2DM), obesity, hypertension, dyslipidemia, and insulin resistance (the so-called metabolic syndrome, MS). MS ultimately leads to the premature development of cardiovascular diseases. In addition, short stature in children and adults, premature adrenarche, and the polycystic ovarian syndrome (PCOS) are endocrinological sequelae of IUGR. (8) Early onset growth delay and prematurity significantly increase the risk for neurological sequelae and motor and cognitive delay.Future prospective studies need to investigate risk factors for infants who are SGA. If reliable prediction can be achieved, there is potential to reduce future perinatal morbidity and mortality, and long term consequences among SGA babies.

Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature

Noonan syndrome (NS), a genetic disease caused in half of cases by activating mutations of the tyrosine phosphatase SHP2 (PTPN11), is characterized by congenital cardiopathies, facial dysmorphic features, and short stature. How mutated SHP2 induces growth retardation remains poorly understood. We report here that early postnatal growth delay is associated with low levels of insulin-like growth factor 1 (IGF-1) in a mouse model of NS expressing the D61G mutant of SHP2. Conversely, inhibition of SHP2 expression in growth hormone (GH)-responsive cell lines results in increased IGF-1 release upon GH stimulation. SHP2-deficient cells display decreased ERK1/2 phosphorylation and rat sarcoma (RAS) activation in response to GH, whereas expression of NS-associated SHP2 mutants results in ERK1/2 hyperactivation in vitro and in vivo. RAS/ERK1/2 inhibition in SHP2-deficient cells correlates with impaired dephosphorylation of the adaptor Grb2-associated binder-1 (GAB1) on its RAS GTPase-activating protein (RASGAP) binding sites and is rescued by interfering with RASGAP recruitment or function. We demonstrate that inhibition of ERK1/2 activation results in an increase of IGF-1 levels in vitro and in vivo, which is associated with significant growth improvement in NS mice. In conclusion, NS-causing SHP2 mutants inhibit GH-induced IGF-1 release through RAS/ERK1/2 hyperactivation, a mechanism that could contribute to growth retardation. This finding suggests that, in addition to its previously shown beneficial effect on NS-linked cardiac and craniofacial defects, RAS/ERK1/2 modulation could also alleviate the short stature phenotype in NS caused by PTPN11 mutations.

Prevalence of Early Growth and Developmental delay in a Rural Community

Background and objectives There is a rise in growth and global developmental delay in children and early intervention will bring down the burden on the society. The present study is to estimate the prevalence of growth and developmental delay and assess the predisposing factors among children aged three years residing in rural communities of Karnataka.Methods About 530 children at three years were assessed for growth and developmental delay. The Ages and Stages Questionnaire ASQ was administered to mothers by a trained interviewer. Growth measurements and hemoglobin estimation were done at the time of developmental evaluation. Socio-demographic characteristics of the families of children were ascertained. Prevalence of global developmental delay was estimated and association between development and maternal child and household characteristics were explored. Physical growth was assessed by using WHO growth charts for weight for age height for age and weight for height. Chi-square test was used to compare categorical variables. Differences were considered significant at Plt0.05 level.Results The results showed that the prevalence of global developmental delay assessed by ASQ was 19.8. Children displayed delay in personal-social 42.5 gross motor 38.1.1 and problem-solving skills 34.9. Maternal educational level was positively associated with communication and problem-solving skills P0.000 while monthly household income was positively associated with communication gross motor and problem-solving skills p0.000.Conclusion The results suggest a high prevalence of developmental delay and poor child health in this rural population. Implementing early intervention programs may ameliorate the long term consequences of these developmental disorders.

Neonatal Nutrition and Consequences on Adult Health

After completing this article, readers should be able to: 1. Describe aberrations in adult health that can result from nutrition in the fetal period and in neonatal life. 2. Review the results of studies from human neonates regarding early nutritional interventions designed for “catch-up” growth. 3. Review results from animal studies regarding early nutrition and “programming” for adult metabolic syndrome. 4. Describe some of the potential epigenetic mechanisms that may be responsible for “programming.” 5. Examine methods for preventing growth delays, the consequences of undernutrition, and the metabolic syndrome related to adverse “programming.” One of the traditional goals of neonatal nutrition is to maintain growth within standardized limits. In the preterm infant, growth between the 10th and 90th percentiles of intrauterine rate has been an ideal goal. More recently, maintenance of lean body mass and bone density; prevention of complications such as chronic lung disease, necrotizing enterocolitis, and infection; and optimization of neurodevelopment and adult health through early nutritional programming have become recognized as more meaningful goals than mere somatic growth. To meet these goals, current nutritional practices require thorough scrutiny in terms of quantity and quality (composition) and how they are customized, if not for the individual patient (which would be ideal), at least for subgroups such as those who are small or appropriate for gestational age, sick or healthy, preterm or term, or male or female. Fetal nutrition and development frequently are used as a template for the low-birthweight infant. A large body of literature on the consequences of fetal undernutrition shows that infants born small for gestational age (SGA) not only have short-term morbidity, but long-term morbidity manifested in what has been termed the “metabolic syndrome.” This syndrome includes abdominal obesity, arterial hypertension, and insulin resistance. Other clinical manifestations can be observed, including thyroid dysfunction, hirsutism, ovarian hyperandrogenism and infertility, dyslipidemia (increased …

First-trimester screening for fetal triploidy at 11 to 14 weeks: a role for fetal biometry

Intrauterine growth restriction in triploidy has been reported as early as in the first trimester. This study was undertaken to evaluate the ability of first-trimester crown rump length (CRL)-based charts to detect triploid fetuses. Analysis of fetal biometry in cases of triploidy diagnosed in the first trimester over the last three years. Biometry for abdominal circumference (AC), head circumference (HC) and biparietal diameter (BPD) was analyzed in relation to both gestational age (GA)-based charts and to CRL-based charts. Five cases of fetal triploidy were diagnosed at 11 to 14 weeks. Screening based on nuchal translucency (NT) and maternal age showed a risk > 1/300 in only one of the 5 cases of triploid fetus. In all of these five cases, CRL-based biometry was grossly abnormal, although it was abnormal in only two of these five cases in relation to GA-based charts. First-trimester CRL-based biometry charts seem to reflect early asymmetrical growth delay in triploidy more accurately than GA-based charts. CRL-based biometry is likely to improve the early detection of triploid pregnancies without leading to dating error.

Cross-Fostering to Diabetic Rat Dams Affects Early Development of Mediobasal Hypothalamic Nuclei Regulating Food Intake, Body Weight, and Metabolism

Exposure to maternal gestational diabetes (GD) "programs" offspring for obesity in childhood and later life. Recent clinical data suggest that neonatal ingestion of breast milk from diabetic mothers might be crucially involved. Mediobasal hypothalamic nuclei such as the ventromedial nucleus (VMN), the paraventricular nucleus (PVN) and the arcuate nucleus (ARC) play a key role in the central nervous system regulation of food intake and body weight. In the ARC, orexigenic neuropeptides such as neuropeptide Y (NPY), galanin (GAL), and agouti-related peptide (AGRP) and anorexigenic neuropeptides such as proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH) are expressed. We investigated the effects of neonatal exposure to milk from GD rat dams on the development of hypothalamic nuclei in weanling rats. Offspring of control (CO) rat dams cross-fostered to GD rat dams (CO-GD) developed early postnatal growth delay. On d 21 of life, CO-GD rats showed structural and functional hypothalamic "malprogramming." The ARC of CO-GD rats showed increased immunopositivity of both NPY and AGRP under basal conditions, despite normal levels of glucose, leptin, and insulin. Conversely, CO-GD rats showed decreased immunopositivity of both POMC and MSH and decreased density of immunopositive neurons, compared with offspring of control rat dams cross-fostered to control rat dams. No morphometric alterations were found in the VMN, whereas CO-GD rats showed an increased total number of neurons in the PVN. In summary, neonatal exposure to maternal diabetes through the intake of dam's milk in rats leads to a complex malprogramming of hypothalamic orexigenic and anorexigenic circuits that are critically involved in the lifelong regulation of food intake, body weight, and metabolism.

How to discriminate between normal and abnormal early pregnancy

Early fetal growth delay and early oligohydramnios have been suspected as signs of embryonal jeopardy. Sonographic examinations of 100 early pregnancies between the sixth and ninth gestational week were performed to investigate predictable sonographic findings of early abortion. Sonographic measurements of the gestational sac (G‐SAC), Crown‐rump length (CRL) and fetal heart rate (FHR) were performed using a transvaginal transducer with Doppler. All measurement of 11 early abortions were compared to those of 89 normal pregnancies to investigate the objective rules for the screening of early abortion. Most of the early aborted pregnancies were classified correctly by discriminant analysis with G‐SAC and CRL (G‐SAC = 0.5222 × CRL + 14.6673 = 0.5 × CRL + 15). In conclusion, early fetal growth retardation and oligohydramnios could discriminate the poor prognosis of early pregnancies.

Hyperglycaemia in vitro alters the proliferation and mitochondrial activity of the choriocarcinoma cell lines BeWo, JAR and JEG-3 as models for human first-trimester trophoblast.

Early intrauterine growth delay in diabetes could be caused by a reduced growth of the placenta. Our study investigates whether hyperglycaemia in vitro reduces trophoblast proliferation. First-trimester trophoblast cell models (BeWo, JAR and JEG-3 choriocarcinoma cells) were cultured for 24 and 48 h with 5.5 mmol/l D-glucose, 25 mmol/1 D-glucose (hyperglycaemia) and with an osmotic control. Cell number, total protein and nucleic acid content and mitochondrial activity (tetrazolium salt assay) were measured, the cell cycle analysed (FACS, cyclin B1 levels) and apoptosis (Annexin-V) measured. In BeWo cells hyperglycaemia reduced cell number, protein, nucleic acid and cyclin B1 levels. The reduced G2/M and increased G0/G1 population after 24 h reflects growth arrest at G0/G1. In JAR cells after 24 h the population was arrested in G0/G1, whereas after 48 h the G0/G1 block was abrogated and the cells were arrested at G2/M. The net effect was an unchanged cell number. In JEG-3 cells hyperglycaemia resulted in fewer cells after 24 h but not after 48 h indicating some adaptation. Mitochondrial activity was either stimulated (BeWo) or reduced (JAR, JEG-3) under hyperglycaemia. Some of these effects were also induced by hyperosmolarity alone. Hyperglycaemia has the potential to inhibit the proliferation of first-trimester trophoblast cell models. The mechanisms leading to growth arrest and to changes in mitochondrial activity are complex and depend on differentiation. We hypothesise a hyperglycaemia-induced impairment of placental growth in the first trimester of a poorly controlled diabetic pregnancy.

Brachmann–de Lange syndrome: a cause of early symmetric fetal growth delay

Brachmann–de Lange syndrome is characterized by pre- and postnatal growth retardation, microbrachycephaly, hirsutism, various visceral and limb anomalies and a typical face. A sonographic prenatal diagnosis at mid-trimester is reported in a case of severe, symmetrical fetal growth delay at 20 weeks gestation, with a thickened skin on the forehead, a small nose and a marked depressed nasal bridge, a long philtrum, micrognathia and a persistently flexed right forearm, with a single bone associated to oligodactyly. Due to the severe mental impairment with a commonly estimated intelligence quotient under 60, the pregnancy was terminated after parental consent.

Diabetes and preimplantation events of embryogenesis.

From animal and human studies is it clear that mammalian embryos are vulnerable to injury during the earliest preimplantation stages of development. Exposure to some agents during this brief period has resulted not only in fetal loss but also in malformations. Thus, the potential for maternal induced embryotoxicity exists earlier than previously expected. This period is marked by a drastic change in metabolic needs at the late morula stage. Glucose becomes the predominant exogenous energy substrate and enters the blastocyst via one of three facilitative glucose transporters, GLUT1, GLUT2, and GLUT3. It has been shown that maternal diabetes adversely affects the preimplantation embryo. Recent work has revealed that hyperglycemia leads to a downregulation of the GLUTs at the blastocyst stage in the mouse. This downregulation results in decreased glucose transport into the blastocyst of diabetic mice and thus lower intraembryonic free glucose levels. The embryos are starving themselves of the key substrate necessary for survival. Maternal diabetes also causes a decrease in the number of cells in rat blastocyst and recently hyperglycemia has been shown to induce apoptosis in the mouse blastocyst via cell death effector pathways involving BAX and caspases. Significant loss of key progenitor cells from the blastocyst may predispose these diabetic embryos to later developmental deficiencies manifesting as dysmorphogenesis, fetal loss or early growth delay. The hypothesis that the hyperglycemia-induced decrease in glucose transport triggers apoptosis is presented and discussed as a novel mechanism to explain preimplantation diabetic embryopathy.

Sonographic criteria for assessment of pregnancies and prediction of miscarriages in first trimester

Transvaginal ultrasound provides an early and accurate technique to assess first trimester pregnancy. Beginning with the demonstration of an intrauterine gestational sac, sonography enables further evaluation of normal pregnancy development, such as identification of the embryo, visualization of the yolk sac, and the presence of fetal cardiac activity as a reassurance of fetal viability. Furthermore it allows closed sonographic monitoring of early intrauterine pregnancy and distinction between normal and abnormal development of pregnancy. A prediction in terms of pregnancy outcome can be made regarding pregnancy complications or specific risks like vaginal bleeding, the demonstration of intrauterine hematoma, advanced maternal age, early growth delay or fetal bradycardia.

Recessive Robinow syndrome: With emphasis on endocrine functions

We present the characteristic features of 14 children with the recessive form of Robinow syndrome and the growth hormone (GH) response to provocation with clonidine and the serum insulin-like growth factor-I (IGF-I) concentration in 12 of these children. The gonadotropin (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) response to gonadotropin-releasing hormone (GnRH) was evaluated in early pubertal and pubertal patients, and the testosterone response to human chorionic gonadotropin (HCG) was evaluated in males. Children with Robinow syndrome, born at full-term, were short at birth (length, 41.4 ± 2.1 cm) and had markedly slow growth velocity (GV) during the first year (13.1 ± 2.1 cm/yr); consequently, they were significantly short at the end of the first year of life (length, 54.4 ± 2.9 cm). This intrauterine and early extrauterine growth delay reflected low growth potential. During childhood, the GV standard deviation score (GVSDS) remained low (− 2.17 ± 0.83). Despite the presence of empty sella in all of the patients, they had an adequate GH response to clonidine provocation (peak, 19.3 ± 5.8 μg/L) and a normal serum IGF-I concentration (309 ± 142 ng/mL) for their age. During childhood and early adolescence, boys with Robinow syndrome had low basal testosterone and a low testosterone response to HCG stimulation (3,000 IU/m 2/d intramuscularly [IM] for 3 days). However, their basal and GnRH-stimulated FSH concentrations were normal. Two girls (Tanner II breast development) had a normal serum estradiol (E2) concentration but high LH and FSH responses to GnRH stimulation. This suggested either defective feedback of E2 on the hypothalamic-pituitary axis or hyporesponsiveness of the ovaries to gonadotropin. Four weeks of HCG therapy (2,500 IU/m 2 IM twice weekly) in three boys with Robinow syndrome increased the penile length and testicular volume, denoting a significant Leydig cell response to prolonged HCG stimulation and the presence of functioning androgen receptors. It is suggested that HCG and/or testosterone therapy during infancy may improve the severe micropenis in these patients.

Early fetal growth delay: is it really predictive of congenital anomalies in infants of diabetic women?

It has been reported that the congenital anomalies frequently observed in offspring of diabetic women may be predicted by first-trimester ultrasound findings that reveal diminution in growth of the embryo/fetus. The aim of the current study was to examine the relationship between early growth delay and congenital anomalies in pregnancies complicated by diabetes. We conducted a retrospective study of 38 patients with insulin-requiring pregestational diabetes mellitus and 81 control pregnancies who had first-trimester ultrasound examinations. A cross-sectional survey of all patients revealed a congenital anomaly rate of 18.4% among the diabetic pregnancies compared to 4.9% among controls (P < 0.02). Early fetal growth delay was defined as a difference of six or more days between the menstrual gestational age and the sonographic gestational age (menstrual age minus ultrasound age). Early growth delay was exhibited in fifteen control pregnancies (18.5%) and eleven insulin-requiring pregestational diabetic pregnancies (28.9%) (P = 0.02). However the incidence of congenital anomalies in these two groups was significantly different, but there was no difference between groups with and without growth delay. The longitudinal growth of two anomalous fetuses of the diabetic group and three anomalous fetuses from the control group was studied. Both groups of fetuses remained within the normal growth range for their respective groups. This study described herein fails to confirm the association of early fetal growth delay with the occurrence of congenital malformations in insulin-requiring pregestational diabetic pregnancies.

Early fetal growth delay: Is it really predictive of congenital anomalies in infants of diabetic women?

Early fetal growth delay: Is it really predictive of congenital anomalies in infants of diabetic women?