Mild Intrauterine Growth Retardation Research Articles

Prenatal diagnosis of a trisomy 7 mosaic case: CMA, CNV-seq, karyotyping, interphase FISH, and MS-MLPA, which technique to choose?

ObjectiveThis study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism.MethodsFor prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD).ResultsAmniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal.ConclusionIn high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7.

Use of infrared thermography to noninvasively assess neonatal piglet temperature.

Hypothermia is risk factor for piglet neonatal mortality, especially for low birth weight piglets. Piglets with intrauterine growth retardation (IUGR) also have a higher mortality risk at birth. This study aimed to validate infrared thermography (IRT) as an alternative to rectal temperature (RT) to measure piglet temperature in the hour postpartum, and to identify piglets with thermoregulation difficulties. At birth (6.3 ± 0.35 min postpartum), 67 piglets were dried, weighed, scored for growth retardation (IUGR; 0–3), and isolated in a plastic box where IRT images were taken, followed by RT. Piglets were then returned to the farrowing pen, and the process repeated at 15, 30, and 60 min postpartum. Piglets were ranked according to their weight (quartiles: 0.57–1.27 kg, 1.27–1.5 kg, 1.5–1.74 kg, 1.74–2.44 kg). Temperatures (ear base and tip; minimum, maximum and average of back) were extracted from IRT images (Thermacam Researcher Pro 2.0). Pearson correlations between temperature measures were calculated, and the effect of time, IUGR score, and weight were included in linear mixed models (SAS 9.4). RT was correlated with all IRT data across time points (P < 0.05); correlations were strongest with the ear base, and weakest with the ear tip and minimum back temperature. Both IUGR score and weight rank affected ear base (P < 0.05) and RTs (P < 0.05). The lightest piglets, and piglets with severe IUGR had the lowest temperature, relative to their counterparts. Indeed, differences between all weights categories were significant for RT. Piglets with the lowest weight (0.27–1.27 kg) had lower ear base temperatures than piglets in the third quartile (1.5–1.74 kg; 35.2 ± 0.36 °C vs. 36.5 ± 0.35 °C, t64.9 = −4.51, P < 0.001) and the heaviest piglets (1.74–2.44 kg; 35.2 ± 0.36 °C vs. 36.4 ± 0.36 °C, t70.4 = −3.97, P < 0.005). Overall, piglets with severe IUGR (score 3) had a lower RT than normal piglets (score 0; 35.8 ± 0.46 °C vs. 37.2 ± 0.42 °C, t43.1 = 3.16, P < 0.05) and piglets with mild IUGR (score 1; 35.8 ± 0.46 °C vs. 37.1 ± 0.40 °C, t45.3 = 2.92, P < 0.05); and they also had lower temperature at the base of the ear than normal piglets (35.1 ± 0.42 °C vs. 36.3 ± 0.36 °C, t63.1 = 3.01, P < 0.05). These results confirmed that IRT is an interesting noninvasive tool for assessing neonatal piglets’ thermoregulatory abilities and could be used in research investigating successful interventions for piglets at risk of hypothermia.

The nature of relationship between some health parameters in infants born with hypoplastic type mild intrauterine growth retardation

Objective. Assessing the relationship between health indicators in infants born with intrauterine growth retardation (JGR) of hypoplastic type of mild severity among themselves, compared with infants born without IGR, and with practically healthy infants from practically healthy mothers.&#x0D; Materials and methods. Under the supervision were 109 infants. From mothers with a burdened somatic and obstetric-gynecological history, 84 children were born: 15 (gr. 1) with mild of hypo-plastic type IGR, 69 (gr. 2) without IGR. The control group (gr. 3) consisted of 25 healthy children born to healthy mothers. All observed babies were born full-term. They were examined in dynamics at the age of 1 (n = 104), 3 (n = 98), 6 (n = 92), 12 (n = 94) months. Outcome recording methods were a comprehensive case history analysis, physical examination, assessment of electrocar-diography and cardiointervalography. Distribution-free statistical analysis methods.&#x0D; Results. A correlation was found at 23 days between weight and body length (r = 0.63), body weight and stress index (r = 0.56), sympathetic activity and stress index (r = 0.84), intraatrial and atrioventricular conductivity (r = 0.64); at 1 month between sympathetic activity and stress index (r = 0.62); at 3 months between weight and body length (r = 0.79), sympathetic activity and stress index (r = 0.87), sympathetic activity and intraventricular conduction (r = 0.67), intraatrial and atrioventricular conduction (r = 0.71); at 6 months between weight and body length (r = 0.81), body weight and intraatrial conduction (r = 0.65), body weight and electric systole (r = 0.58), sympathetic activity and stress index (r = 0.92); at 12 months between body length and intraatrial (r = 0.74), body length and atrioventricular conduction (r = 0.76), sympathetic activity and stress index (r = 0.94), sympathetic activity and electrical systole (r = 0.71), stress index and intraventricular conduction (r = 0.68), stress index and electric systole (r = 0.69), intraatrial and stress index (r = 0.9), atrioventricular conduction and electric systole (r = 0.63).&#x0D; Conclusions. The revealed correlation communications between of some studied parameters allow doctors to allocate groups of dispensary observation, to diagnose changes at early stages of the pathological process, conduct correctional actions with assessment of their efficiency.

Refining the phenotypical and mutational spectrum of Taybi-Linder syndrome.

Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. RNU4ATAC is transcribed into a non-coding small nuclear RNA which is a critical component of the minor spliceosome. We report here four foetuses and four unrelated patients with RNU4ATAC mutations. We provide antenatal descriptions of this rare syndrome including unusual features found in two twin foetuses with compound heterozygosity for two rare mutations who presented with mild intrauterine growth retardation and atypical dysmorphic facial features. We also carried out a literature review of the patients described up to now with RNU4ATAC mutations, affected either with TALS or Roifman syndrome, a recently described allelic disorder.

Plac1 (placenta‐specific 1) is essential for normal placental and embryonic development

Plac1 is a recently identified, X-linked gene whose expression is restricted primarily to cells of the trophoblast lineage. It localizes to a chromosomal locus previously implicated in placental growth. We therefore sought to determine if Plac1 is necessary for placental and embryonic development by examining a mutant mouse model. Plac1 ablation resulted in placentomegaly and mild intrauterine growth retardation (IUGR). At E16.5, knockout (KO) and heterozygous (Het) placentae of the Plac1-null allele inherited from the mother (X(m-) X) weighed approximately 100% more than wildtype (WT) placentae, whereas the corresponding embryos weighed 7-12% less. Histologically, Plac1 mutants exhibited an expanded spongiotrophoblast layer that invaded the labyrinth. By contrast, Het placentae that inherited the null allele from the father (XX(p-) ) exhibited normal growth and were histologically indistinguishable from WT placentae, consistent with paternal imprinting of Plac1. When examined across gestation, WT and X(m-) X placental weights peaked at E16.5 and decreased slightly thereafter. KO placentae (X(m-) X(p-) and X(m-) Y), however, continued to increase in weight after E16.5, consistent with a functional role for the paternal Plac1 allele. Subsequent analysis confirmed that the paternal allele partially escapes complete X-inactivation and thus contributes to placental growth regulation. Additionally, although male Plac1 KO mice can survive, they exhibit decreased viability as a consequence of events occurring late in gestation or shortly after birth. Thus, Plac1 is a paternally imprinted, X-linked gene essential for normal placental and embryonic development.

Evaluation of maternal infusion therapy during pregnancy for fetal development

The aim of this project was to study the possible association between maternal infusion treatments during pregnancy and variables of fetal development as well as the occurrence of congenital abnormalities (CA) in a case-control design. The large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) was evaluated based on the medically recorded infusion treatment during pregnancy. Of 22,843 case pregnant women who had newborns or fetuses with congenital abnormalities, 112 (0.5%), while of 38,151 control pregnant women who had newborn infants without any defects, 262 (0.7%), had infusion treatment during pregnancy. Infusion treatment was more frequent in the control group than in the case group with congenital abnormalities (adjusted POR with 945 95% CI: 0.7, 0.6-0.9) and there was no higher rate of maternal infusion treatments in any congenital abnormality group. Mean gestational age was shorter and mean birth weight was smaller in control newborn infants without CA born to mothers with infusion treatment during pregnancy than in the babies of mothers without infusion treatment. The prevalence of mild intrauterine growth retardation was more frequent in the fetuses of pregnant women with hyperemesis gravidarum treated with infusion. The results of the study suggest that infusion treatment of pregnant women did not associate with a higher risk of congenital abnormalities. In addition, the intravenous infusion of drugs has some, but limited efficacy to prevent the adverse effects of hyperemesis gravidarum and threatened preterm delivery.

The Importance of Head Growth Patterns in Predicting the Cognitive Abilities and Literacy Skills of Small-for-Gestational-Age Children

This study evaluated the effects of head growth compromise beginning in utero and continuing, in some cases, through the first 9 months of life on the cognitive and literacy skills of school-age small-for-gestational-age (SGA) children. Seventy-one SGA children, aged 7 to 9 years (gestational ages, 24-41 weeks) and 16 full-term appropriate-for-gestational-age control children of comparable socioeconomic backgrounds and age at testing completed tests assessing intelligence, receptive language, working memory, problem solving, visual-motor integration, phonological awareness, reading, and spelling. SGA children were subdivided into head-growth pattern groups based on their head circumference at birth and at 9 months postterm. Analyses showed that SGA children with poor prenatal and postnatal head growth had the worst outcomes, followed by those with prenatal brain compromise, but good postnatal head growth. SGA children with preserved head growth in utero as well as good head growth after birth demonstrated the best outcomes, although spelling skills were deficient relative to full-term peers. The Verbal and Full Scale IQ ratings of the SGA children who had experienced brain compromise in utero declined significantly from 5 to 8 years of age. We conclude that mild intrauterine growth retardation (IUGR) has a minimal effect on the development of cognitive or academic abilities, providing that brain growth in utero is not affected. IUGR that slows brain growth in utero impairs the acquisition of some cognitive and academic abilities, even when followed by good catch-up head growth after birth, whereas poor brain growth in utero followed by little or no catch-up head growth results in widespread impairments. Findings highlight the limits to brain plasticity and emphasize the importance of optimal prenatal and postnatal brain growth.

Study of developmental abnormalities and deaths after human zygote exposure

Experimental studies indicated that the mouse zygote is susceptibel to experimental induction of developmental anomalies including defects (mainly hydrops), growth retardation and mid- and late-gestational death with certain mutagenic agents. The material of the Hungarian Optimal Family Planning Program is appropriate to check this finding in a human material because participants were asked to visit the coworkers of the Program immediately after the first missed menstrual period and data concerning potentially hazardous environmental factors were obtained. At that time participants were immediately after the pre-and implantation period and they had no knowledge about their pregnancy outcomes. In 1994 the data of their pregnancy outcomes are available. Of 5453 evaluated pregnancies, 1167 were selected for this study because they visited the coworkers of the Program within 28 days post conception. Of 1167 pregnancies, 316 (27%) were exposed to some environmental factors, mainly drugs. A mild intrauterine growth retardation was found in the exposed group. The rate of congenital abnormalities and infant death did not differ between the exposed and unexposed groups. The detailed analysis of different congenital abnormality groups also did not show any significant difference between the exposed and unexposed groups. These negative results are explained by the fact that the observed environmental factors are not mutagenic, at least not in the dosage which was used, or the human zygote is not sensitive to mutagenic agents in the post-conceptional days.

Maternal hyperoxygenation in the treatment of mild intrauterine growth retardation: a pilot study.

The aim of this study was to determine the efficacy of long-term maternal hyperoxygenation in comparison with bed rest in the management of mildly growth-retarded fetuses (5-10th centile).Thirty-eight patients with intrauterine growth retardation were studied. The patients were divided into oxygen-treated (n = 18) and untreated (n = 20) groups. Ultrasound assessment of amniotic fluid volume was performed on alternate days, and the fetal abdominal circumference was evaluated weekly. Doppler analysis of fetal/maternal circulation was performed upon the patient's arrival at hospital, after 12 h, and thereafter on alternate days until parturition. Fetal blood was sampled by cordocentesis for immediate blood gas analysis at the start of the study and on the day of delivery. Although in the treated patients there was significant improvement in Doppler flow pat tern and blood gas indices, no significant differences in type of delivery and perinatal outcome were noted between the groups. Maternal hyperoxygenation in mild intrauterine growth retardation did not improve perinatal outcome.

Antenatal Treatment of Neonatal Alloimmune Thrombocytopenia

Neonatal alloimmune thrombocytopenia results from the formation of a maternal antibody to a paternal antigen on fetal platelets. Intracranial hemorrhage, which may be antenatal, occurs in approximately 15 to 20 percent of infants with this form of thrombocytopenia. In families with an affected infant, 75 percent of subsequent infants are affected. We report the results of antenatal treatment with intravenous gamma globulin, with or without dexamethasone, in seven pregnant women who had previously had infants who had severe alloimmune thrombocytopenia. The platelet count increased by a mean (+/- SD) of 72.5 +/- 62 x 10(9) per liter in the six fetuses in whom periumbilical blood sampling was performed. All seven treated fetuses had platelet counts above 30 x 10(9) at birth, and none had an intracranial hemorrhage, in contrast to all seven of their respective untreated siblings, who had lower platelet counts and three of whom had intracranial hemorrhages (antenatal in two infants). Mild intrauterine growth retardation was observed in one treated infant; all seven infants have developed normally in the two months to four years since birth. We conclude that intravenous gamma globulin, with or without dexamethasone, is effective in elevating the fetal platelet count in severe cases of neonatal alloimmune thrombocytopenia and in helping to avoid intracranial hemorrhage.

Growth and Fatty Acid Metabolism in Experimental Intrauterine Growth Retardation: Effect of Postnatal Nutrition in Rat

Rats, 3½ to 4 d of age, were used to study weight gain and fatty acid (FA) metabolism as a function of degree of intrauterine growth retardation (IUGR) and of postnatal nutrition. The IUGR, quantified postnatally as mild and severe, was produced by uterine artery ligation on d 17 of gestation, and controls were sham-operated. Food intake was manipulated by varying the litter size; i.e., pup number per dam was 4 or 5 for overfeeding, 8–10 for normal feeding and 13–15 for underfeeding. Fatty acid synthesis rate (FASR) (determined by tritiated water incorporation in FA) and contents were determined in selected organs at 84 to 96 h of age. The initial weights (grams) at 2 to 12 h of age were: 5.88 ± 0.74 (mean ± SD) for controls, 5.18 ± 0.11 for mild IUGR and 4.18 ± 0.24 for severe IUGR. During the first 96 h of life, weight gain was less in underfed control pups while overfeeding resulted in the same weight gain as in normally fed pups. Pups with mild IUGR showed the same effect of under- or overfeeding as control pups. In the severe IUGR groups, weight gains were similar in all three feeding groups. In the carcass, the fatty acid content was reduced as a result of both prenatal and postnatal undernutrition. Although the underfed control group had a high FASR, underfeeding had no effect on the FASR of groups with IUGR. In the liver, the FA content was also lower in the underfed controls and in IUGR groups, without any difference in FASR. Feeding did not influence the FASR of liver. In the brain, the FA synthesis rate of normally fed IUGR pups was significantly greater and was almost twice as high in underfed IUGR pups as in normally fed IUGR pups. This was accompanied by significantly lower FA contents in both normally fed and underfed IUGR pups. It is concluded that in the rat, during the first few days of life, 1) a generous food supply does not augment weight gain, 2) a restricted food supply reduces weight gain in normal and mild IUGR but not in severe IUGR and 3) the reduction fatty acid content in prenatal and postnatal under-nutrition is consistent with the reduction in weight gain.

246 GROWTH AND FATTY ACID METABOLISM IN EXPERIMENTAL INTRAUTERINE GROWTH RETARDATION: EFFECTS OF POSTNATAL NUTRITION

Growth rate and fatty acid (FA) metabolism were evaluated in the first 3½ days of life in rats as a function of degree of intrauterine growth retardation (IUGR) and of postnatal nutrition. IUGR (mild, BW≤1 SD and severe, BW≤2 SD) was produced by uterine artery ligation on 18th day of gestation, and controls were sham operated. Food intake was manipulated by varying the litter size per dam; n=16 for underfeeding, n=10 for normal feeding and n=4 for overfeeding. The growth rate in the control pups was reduced by underfeeding while overfeeding and normal feeding resulted in the same rate. The mild IUGR responded the same way as in control. In severe IUGR group, the growth rate was similar regardless of the feeding protocol. The fatty acid content in carcass was reduced as a result of either prenatal or postnatal undernutrition in spite of a higher fatty acid synthesis rate (FASR) (tritiated water technique). In liver and lung, there was no difference in FASR between controls and IUGR and feeding did not influence the rate; the fat content was lower in under fed control and in IUGR rats. In the brain, FASR of normal fed IUGR was markedly higher and the rate almost doubled in underfed IUGR. This was accompanied by significantly less FA contents in both normal fed and under fed IUGR group. We conclude that postnatal undernutrition retards postnatal growth of normal and mildly affected IUGR rats, but no additional growth retardation was observed in the severely affected IUGR pups. The changes in fatty acid metabolism in various organs studied were consistent with the alterations in growth.

A six-months' follow-up study of growth, morbidity and functional immunity in low birth weight neonates with special reference to intrauterine growth retardation in small-for-gestational-age infants.

The immunologic functions in preterm (PT) and small-for-gestational-age (SGA) babies from birth till 6 months of age was assessed and their nutritional status and morbidity were studied. Sera were collected from 50 infants of both sexes at birth and at 3 and 6 months of age. 20 were full-terms 15 PT and 15 SGA. Measurements were made of body weight; body height; head chest and midarm circumference; and skinfold thickness. Serum immunoglobulin and C3 complement levels were estimated by Martins technique. Neutralizing antibody (NA) against vaccinia virus acquired transplacentally by the neonates was estimated in the cord blood. Cellular immunity against vaccinia virus at the 1st month of life was assessed by studying the kinetics of vesiculation and pustulation following smallpox vacciantion. At 3 and 6 months delayed cutaneous hypersensitivity (DHR) was studied by intradermal injections of old tuberculin streptokinase streprodornase 0.1 ml candida antigen and 0.1 ml heat-killed smallpox vaccine. Among the 3 groups of infants PT were the smallest and their average birth weight the lowest. PT had a higher growth rate than SGA. 8 SGA babies caught up to full-terms but the remaining 7 were still light. Immunoglobulins were measured in blood as was NA. SGA babies had impaired early IgA and IgM synthesis which may be due to intrauterine undernutrition. Specific CMI was poor in PT neonates but adequate in SGA babies. Both term and PT babies at 3 months showed comparable DHR against various recall antigens. However it was impaired in only 5 SGA babies which persisted up to 6 months of age. Severe intrauterine growth retardation (IUGR) was found in 5 SGA infants who had a mean birth weight of 1.86 kg. The remaining 10 those with a mean birth weight of 2.2 kg. had mild IUGR. CMI seemed to mature poorly in these 5 severely affected infants.

ANATOMIC FEATURES OF GROWTH FAILURE IN CONGENITAL HEART DISEASE

A quantitative study was undertaken of body size, organ size, and cellular structure in 220 individuals dying with congenital heart disease. Infants dying in the perinatal period had evidences of a mild intra-uterine growth retardation. Infants 1 month to 8 years of age had organ and cellular abnormalities closely resembling those usually found with chronic undernutrition. Older individuals dying with congenital cardiac malformations had organ and cellular abnormalities which may be related to chronic hypoxia.