Bone ultrasound velocity of infants born small for gestational age.

BACKGROUND: Quantitative ultrasound is increasingly used to assess bone status. Bone speed of sound (SOS), a biophysical property of bone, has been used to predict bone breakability. While decreased bone mineral content and delayed epiphyseal growth have been reported in small for gestational age (SGA) infants, there are no data on bone SOS in this group of infants. OBJECTIVE: To test the hypothesis that SGA infants have lower bone SOS than appropriate for gestational age (AGA) infants. METHODS: Bone SOS was measured within the first 96 hours of life at the right tibial midshaft in 22 singleton SGA infants. We compared these data with data obtained in 73 AGA controls. We used the Omnisense instrument which measures axially transmitted SOS. Infants ranged in gestational age (GA) from 25 to 42 weeks and in birth weight (BW) from 500 to 2,585 g. Statistical analyses included paired t-tests between the actual value obtained in every child and the theoretical, computed average normal value for GA, BW, or knee-sole length (KSL) based on our curves for AGA singletons. A p value < 0.05 was considered significant. RESULTS: Bone SOS measured in SGA infants was higher than the predicted computed average SOS of AGA singletons with significant differences in all of the parameters studied. CONCLUSIONS: Contrary to our hypothesis, SGA infants have higher bone SOS than AGA controls. Since bone mineral density is reported to be low in these infants, we speculate that intrauterine growth restriction may affect bone mineral density and bone protein matrix in opposite directions.

[Preterm labor and IUGR rates in patients with cardiac anomalies in the material of the Pregnancy Pathology Unit at the Jagiellonian University OB/GYN Department between 1986-1999]. / Czestosc porodów przedwczesnych i hipotrofii w grupie pacjentek z wadami serca w materiale Oddzialu Patologii Ciazy Katedry Ginekologii i Poloznictwa Collegium Medicum Uniwersytetu Jagiellonskiego w latach 1986-1999.

INTRODUCTION: Advance in medicine in general caused more and more women with cardiac defects reach reproductive age. AIM: Analysis of kind and advance of cardiac disease influence on preterm labour and IUGR rates. MATERIAL AND METHODS: A prospective study on 232 pregnant patients with cardiac malformations, who were hospitalised in Pathology of Pregnancy Unit of OB./ GYN Jagiellonian University Clinic was performed between 1986-1999. Acquired data were compared with results obtained from control group of 424 pregnant patients with physiological course of pregnancy. RESULTS: Results prove of shorter pregnancy duration in patients with higher NYHA classes. Preterm labour rate in patients of NYHA III and IV equals to 31.15% and is 3 times higher than in control group. Patients of NYHA I and II revealed comparable gestational age with control group. CONCLUSIONS: Worse obstetric outcome is characteristic for 3rd and 4th NYHA classes. Intrauterine growth retardation in patients with cardiac malformations occurs after 34 week of pregnancy.

Endocrine and metabolic consequences of intrauterine growth retardation.

Size at birth and early infancy growth rates have been linked to long-term risks for diseases, such as type 2 diabetes and cardiovascular disease. These associations could be explained by permanent programming of metabolic responses and selective survival of those genetically predisposed to such adaptations. These epidemiologic associations may also affect long-term disease risk in short small-for-gestational age children, who are often treated with growth hormone. Study of the mechanisms and genetic factors involved in the association between small size at birth, rapid postnatal weight gain, and adult disease may promote the early identification of subjects with the highest disease risk and new opportunities to develop targeted early interventions.

Feeding growth restricted preterm infants with abnormal antenatal Doppler results.

Absence or reversal of end diastolic flow (AREDF) in the umbilical artery is associated with poor outcome, and elective premature delivery is common. Feeding these infants is a challenge. They often have poor tolerance of enteral feeding, and necrotising enterocolitis may develop. This review explores current practice to see if there is evidence on which to base guidelines. The incidence of necrotising enterocolitis is increased in infants with fetal AREDF, especially when complicated by fetal growth restriction. Abnormalities of splanchnic blood flow persist postnatally, with some recovery during the first week of life, providing justification for a delayed and careful introduction of enteral feeding. Such a policy exposes babies to the risks of parenteral nutrition, with no trials to date showing any benefit of delayed enteral nutrition. Trials are required to determine the optimum timing for introduction of enteral feeds in growth restricted infants with fetal AREDF.

[Triploidy: prompt diagnosis based on typical clinical signs in a live-born extremely low birth-weight infant]. / Triploidie: Rasche Diagnosestellung anhand der typischen klinisch erhobenen Stigmata eines lebend geborenen extrem kleinen Frühgeborenen.

A child with complete triploidy is rarely born alive. However, owing to the advances in perinatal medicine even extremely immature preterm infants receive full support in the delivery room and are admitted to the neonatal ICU. Consequently, the clinician may also have to consider the diagnosis of triploidy when faced with a dysmorphic extremely preterm infant. We report here the smallest described live born girl of 25 + 5 weeks of gestational age with typical clinical findings of complete triploidy phenotype II. The aim of the case report is to make the neonatologist aware of this syndrome using photographs of this case as well as discussing the literature available. Prompt clinical diagnosis confirmed by chromosome analysis helps doctors and parents with the decision whether to continue promising or to limit futile life support measures.

[Foeto-foetal conflict of interests in multiple pregnancies with severe discordant growth; ethical dilemmas]. / Foeto-foetaal belangenconflict bij een meerlingzwangerschap met ernstig discordante groei; ethische afwegingen.

Two pregnant women, 19 and 26 years old, presented at the beginning of the third trimester with one growth-retarded foetus in a multiple pregnancy. Both cases were managed conservatively. In the first woman, one foetus died at 30 weeks of gestation, after the mother developed pre-eclampsia. After the death of the impaired foetus pre-eclampsia resolved and the second child was born healthy at 36 weeks of gestation. The second woman had triplets with one severely growth-retarded foetus. This foetus died at 3I weeks of gestation. At 33 & 317 weeks, caesarean section was performed on both maternal and foetal indications. Two healthy premature neonates were born. In multiple pregnancy with discordant growth, the interests of the foetuses may be in opposition, which creates an ethical dilemma. This may be resolved by carefully addressing the interests of all those involved and keeping in mind the prognosis, duration of pregnancy and the best interests of the healthy foetus, which should not be harmed by intervention. Therefore, active intervention is not always the best option; the least harm it does is increasing the risk ofpreterm birth.

Fetal origins of insulin resistance and obesity.

A number of epidemiological studies worldwide have demonstrated a relationship between poor early growth and an increased susceptibility to insulin resistance, visceral obesity, type 2 diabetes and other features of the metabolic syndrome in adulthood. However, the mechanistic basis of this relationship and the relative roles of genes and the environment remain a subject of debate. The 'thrifty phenotype' hypothesis proposes that poor fetal nutrition leads to programming of metabolism and an adult phenotype that is adapted to poor but not plentiful nutrition. The maternal reduced-protein rat model has been used to examine the importance of the maternal environment in determining susceptibility to adult disease. Pregnant and lactating rat dams are fed a diet containing 80 g protein/kg as compared with 200 g protein/kg, which leads to growth restriction in utero. Offspring of low-protein dams have increased susceptibility to diabetes, insulin resistance and hypertension when fed a palatable high-fat diet that promotes obesity. Administration of leptin during pregnancy and lactation to these protein-restricted dams produces offspring that have increased metabolic rate and do not become obese or insulin resistant when fed on a high-fat diet. Increased glucocorticoid exposure, particularly during late gestation, has been linked with insulin resistance in adulthood. High levels of fetal glucocorticoids may result from a decreased activity of placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2, which normally protects the fetus from high maternal glucocorticoid levels. Leptin administration to protein-restricted dams inhibits the suppression of 11beta-HSD-2 and may be one mechanism by which the metabolic syndrome is prevented.

Experimental intrauterine growth retardation in the rat causes a reduction of pancreatic B-cell mass, which persists into adulthood.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the possibility that intrauterine growth retardation (IUGR) causes alterations of glucose tolerance, insulin secretory response to glucose, and pancreatic B-cell growth, and if such changes may persist into adulthood. METHODS: Pregnant rats were operated on day 16 of pregnancy ad modum Wigglesworth to induce IUGR. Operated rats gave birth to viable offspring but litter size was reduced. The mothers nursed their pups, which were subsequently weaned and reared to an age of 3 months in apparent good health. RESULTS: At 1 day of age, IUGR pups were 10% lighter than control newborns whose mothers had been subjected to a sham operation. Pancreatic B-cell mass and insulin content were reduced by 35-40% in newborn IUGR offspring. Postnatal growth did not differ between IUGR and control animals of either sex and the difference in body weight at birth was not apparent from 1 week of age and onwards. Tests performed at 3 months of age could not demonstrate differences in glucose tolerance between IUGR and control animals. In females, but not in males, the peak insulin secretory response to glucose was lower in IUGR animals compared to controls. In the 3-month-old rats, B-cell mass was reduced by 40% in male and by 45% in female IUGR rats compared to controls, a reduction corresponding to a similar decrease in pancreatic insulin content (male reduction 48%, female reduction 45%). CONCLUSIONS: In the rat, IUGR causes a diminution of pancreatic B-cell mass which persists into adulthood. Normal glucose tolerance could be maintained but it is conceivable that increasing demands on insulin secretion may not be met by the reduced B-cell mass and that impaired glucose tolerance and even diabetes would hence develop.

Intrauterine growth restriction-etiology and consequences: what do we know about the human situation and experimental animal models?

Embryonic and fetal growth depend on genetic and environmental factors, and the process is the result of the interaction between these factors. About 7-9% of live-born infants have a birth weight below normal (below the 10th percentile). The rate and extent of intrauterine growth restriction (IUGR) varies by ethnicity and socio-economic status. Some of the suspected causes of IUGR are as follows. (1) Maternal factors such as inadequate or severe malnutrition, chronic maternal diseases, birth order, multiple births, and parental genetic factors. (2) Placental pathology, mainly placental vascular damage that may lead to placental insufficiency. This is often found in maternal diseases such as pre-eclampsia, and Thrombophilia. (3) Intrauterine infections and specific fetal syndromes, including chromosomal aberrations. (4) Non-classified causes such as adolescent's pregnancy, maternal smoking and alcohol drinking, living at high altitudes. Several existing animal models for IUGR, including uterine artery ligation or gene knock out models, although insightful of potential mechanism(s) underlying intrauterine growth restriction, are limited in that they do not reflect human causality. As the ultimate goal is prevention, we seem still to be distant from achieving this goal.

Fetal growth restriction associated with measles virus infection during pregnancy.

We report on a 28-week infant with growth restriction starting after 23 weeks' gestation because of measles virus (MV) infection of the mother. Histological findings for the placenta revealed extensive fibrin deposition and necrosis of the villi, and MV antigen was demonstrated in the syncytiotrophoblast by immunostaining. The MV-specific IgM level in the infant was negative, but that of the mother was positive. Therefore, we speculate that growth restriction is not attributed to direct infection with MV, but to placental dysfunction due to a decrease in intravillous blood flow and oxygen supply to the fetus.

Case gender and severity in cerebral palsy varies with intrauterine growth.

BACKGROUND: There is an unexplained excess of cerebral palsy among male babies. There is also variation in the proportion of more severe cases by birth weight. It has recently been shown that the rate of cerebral palsy increases as intrauterine size deviates up or down from an optimum about one standard deviation heavier than population mean weight-for-gestation. AIMS: To determine whether the gender ratio or the severity of cases also varies with intrauterine size. METHODS: A total of 3454 cases of cerebral palsy among single births between 1976 and 1990 with sufficient data to assign case severity (based on intellectual impairment and walking ability) and to compare weight-for-gestation at birth to sex specific fetal growth standards, were aggregated from nine separate registers in five European countries. RESULTS: The greater the degree to which growth deviates either up or down from optimal weight-for-gestation at birth, the higher is the rate of cerebral palsy, the larger is the proportion of male cases, and the more severe is the functional disability. Compared to those with optimum growth the risk of more severe cerebral palsy in male babies is 16 times higher for those with a birth weight below the 3rd centile and four times higher when birth weight is above the 97th centile. In contrast, for mild cerebral palsy in female babies the excess risks at these growth extremes are about half these magnitudes. CONCLUSIONS: Among singleton children with cerebral palsy, abnormal intrauterine size, either small or large, is associated with more severe disability and male sex.

Epidural local anesthetics: a novel treatment for fetal growth retardation?

BACKGROUND: Chronically compromised uterine perfusion may lead to placental insufficiency and subsequent intrauterine growth restriction (IUGR). Various therapeutic approaches (e.g. vasodilators, low-dose aspirin, intravenous glucose infusion, and hemodilution) are often of limited efficacy. Local anesthetics have been shown to improve placental blood flow in pre-eclamptic women. We hypothesized that epidural administration of local anesthetics might improve outcome in IUGR independent of the underlying cause. In preparation for a clinical trial to test this hypothesis, we performed a pilot study in 10 patients. METHODS: After approval of the study protocol, 10 pregnant women presenting with oligohydramnios and IUGR were included in the study. In addition to our standard protocol (magnesium, glucose, betamethasone), each patient received an epidural catheter (T10/T12) with continuous infusion of bupivacaine 0.175% at a rate of 5 ml/h. Uteroplacental circulation was monitored by Doppler sonography and the amount of amniotic fluid was estimated daily. RESULTS: Epidural insertion and infusion was performed without complications. Four patients continued to deteriorate rapidly, amniotic fluid volume did not change and uterine artery pulsatility index (PI) tended to increase. In the remaining 6 patients the clinical status stabilized, amniotic fluid volume tended to increase and uterine artery PI tended to decrease during treatment. This improvement was associated with a prolonged interval to cesarean section and increased infant birth weight. CONCLUSION: Our data suggest that, even if the underlying cause of IUGR is not pre-eclampsia, epidural local anesthetic administration might improve placental blood flow and be beneficial in a subgroup of patients. A clinical trial to test this hypothesis appears warranted.

Prenatal risk factors for severe retinopathy of prematurity among very preterm infants of the Australian and New Zealand Neonatal Network.

OBJECTIVE: To identify prenatal and perinatal risk factors for clinically severe (stage 3 or 4) retinopathy of prematurity (ROP). METHODS: Data were collected prospectively as part of the ongoing Australian and New Zealand Neonatal Network audit of high-risk infants (birth weight of <1500 g or gestational age [GA] of <32 weeks) admitted to a level III neonatal unit in Australia or New Zealand. Prenatal and perinatal factors to 1 minute of age were examined for the subset of infants with GA of <29 weeks who survived to 36 weeks' postmenstrual age and were examined for ROP (n = 2105). The factors significantly associated with stage 3 or 4 ROP were entered into a multivariate logistic regression model. RESULTS: Two-hundred three infants (9.6%) had stage 3 or more ROP. Prematurity was the dominant risk factor, with infants with GA of <25 weeks having 20 times greater odds of severe ROP than infants with GA of 28 weeks. Birth weight for GA also had a "dose-response" effect; the more growth-restricted infants had greater risk, with infants below the 3rd percentile of weight for GA having 4 times greater odds of severe ROP than those between the 25th and 75th percentiles. Male gender was also a significant risk factor (odds ratio: 1.73; 95% confidence interval: 1.25-2.40). CONCLUSIONS: These data, for a large, essentially population-based cohort, suggest that factors related to the degree of immaturity, intrauterine growth restriction, and male gender contribute to severe ROP.

The probability of giving birth among women who were born preterm or with impaired fetal growth: a Swedish population-based registry study.

The primary aim of this study was to investigate whether women born prematurely or with impaired fetal growth have a reduced probability of giving birth. Using Swedish population-based registries, the authors identified 148,281 women born in 1973-1975 for follow-up until 2001. Of these women, 4.1% were born preterm and 0.32% very preterm, 0.29% were born with a very low birth weight, and 5.4% were small for gestational age. Outcome measures were the hazard ratios for giving birth during the study period. Adjustments were made for socioeconomic factors. Very-low-birth-weight women displayed a reduced probability of giving birth (hazard ratio = 0.74, 95% confidence interval: 0.60, 0.91), most apparent among women aged 25 or more years. There were also tendencies of reduced hazard ratios of giving birth among women born preterm or very preterm in this age interval. Women born small for gestational age (below -2 standard deviations) seemed to be more likely to have given birth (hazard ratio = 1.09, 95% confidence interval: 1.04, 1.14), but when a more extreme group of small-for-gestational-age women (below -3 standard deviations) was defined, the association was less evident (hazard ratio = 1.04, 95% confidence interval: 0.94, 1.16). The results suggest that very-low-birth-weight women and, possibly, women born preterm or very preterm have a reduced probability of giving birth, while the results regarding small for gestational age are less clear.

Prevalence of cranial scan abnormalities in preterm twins in relation to chorionicity and discordant birth weight.

OBJECTIVE: The purpose of this study was to determine the incidence of ultrasonographically detected cerebral white matter lesions (WMLs) in preterm twins at birth in relation to chorionicity, discordant weight and twin-twin transfusion syndrome (TTTS). METHODS: In this retrospective study, perinatal, neonatal, and cranial scan data of 85 monochorionic (MC) and 94 dichorionic (DC) twin pregnancies (341 infants) delivered between 24 and 34 weeks of gestation were collected. Data were analysed according to chorionicity, discordant birth weight (>20%), single intrauterine death and TTTS. RESULTS: The cerebral WML was seen in 14% of preterm twins. Monochorionic infants had higher risks of WML than DC twin (odds ratio 7.1; 95% CI 3.28-15.8). In MC group, discordant weight (37%), TTTS (38%), single intrauterine death (67%) had higher incidence of cerebral WML than concordant weight infants (7%). Similarly, incidence of WML was higher in DC discordant compared with concordant weight infants (13% versus 2%; P < 0.05). CONCLUSION: Monochorionic infants had a seven-fold higher incidence of cerebral WML than DC infants. Discordant birth weight, TTTS and survivor of co-twin demise are an independent risk of cerebral white matter lesion.

Clinical consequences of first-trimester growth discordance in twins.

OBJECTIVES: To evaluate the clinical consequences of size discordance in the first-trimester of pregnancy in twins. STUDY DESIGN: This study was performed in a university tertiary referral centre. Nineteen pairs of twins identified as discordant were compared with 41 concordant twins. The rates of intrauterine growth restriction (IUGR), congenital malformations, and growth discordance in late pregnancy and at delivery were compared using chi-squared test and Fisher's exact test. RESULTS: There was not a significant difference in the rate of congenital malformations between the studied groups. The rates of IUGR and fetal growth discordance in late pregnancy were significantly higher in the first-trimester discordant group (57.2 and 35.7%, respectively) than in the control group (24.4 and 7.3%; P = 0.03 and 0.02, respectively). CONCLUSIONS: First-trimester growth discordant twins have an increased risk of IUGR and growth discordance in late pregnancy, and therefore they are a high-risk subgroup among multiple pregnancies.