Endocrine regulation in asymmetric intrauterine fetal growth retardation.

OBJECTIVE: The ponderal index (PI) is a widely accepted measure of disproportionate growth or asymmetrical growth retardation by pediatricians worldwide. Identification of disproportionately grown small for gestational age (SGA) neonates by using the ponderal index as a measure of the nutritional status at birth, is important because they constitute a high-risk group among SGA neonates. Poor nutritional status of the mother could have a direct effect on the organs of the developing fetus and/or affect the endocrine milieu in the maternal feto-placental unit resulting in an increased incidence of intrauterine growth-retarded (IUGR)/SGA births. IUGR is a significant risk factor for adult disease. In this study, we have investigated the endocrine adaptation by the fetus to overcome the growth disadvantage caused due to poor nutritional status of the mother. MATERIALS AND METHODS: We examined the quantitative variations in hormonal and growth factor profiles in paired maternal and cord blood samples obtained from mothers and their neonates who were classified based on their growth status into SGA and appropriate for gestational age (AGA). RESULTS: (1) A total of 24.7% neonates had a PI < 2, indicating a high incidence of asymmetric IUGR in the population studied. (2) Anthropometric parameters measured in the mothers indicate that the mothers giving birth to neonates with a PI < 2 had poor nutritional status, both prior to and during pregnancy. (3) We observed increased levels of placental lactogen and prolactin and decreased levels of insulin in the cord blood of neonates with PI < 2, while lower levels of insulin-like growth factor 1 (IGF-1) and higher levels of epidermal growth factor (EGF) were observed in their mothers. CONCLUSION: Poor maternal nutritional status results in fetal adaptation to a growth restricted environment via the modulation of the pituitary-thyroid axis thereby altering the endocrine milieu, thus affecting fetal growth.     

Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate

Objective.?Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia.

Study design.?This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.

Results.?(1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups (p?<?0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r?=?0.48, p?=?0.04).

Conclusion.?Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.     

Birthweight in pregnant women with protein S deficiency treated with low-molecular-weight heparin: a retrospective cohort study

Objective: To determine the risk of small-for-gestational-age (SGA) and intrauterine growth retardation (IUGR) in pregnant women with protein S (PS) deficiency who received low-molecular-weight heparin (LMWH).

Methods: Retrospective cohort study of pregnant women seen from January 2002 to December 2011. The study cohort comprised a total of 328 patients with PS deficiency, who received prophylactic enoxaparin during pregnancy. The control cohort included 11 884 pregnant women without significant past medical history. The risk of SGA and IUGR was calculated as odds ratio. Multivariate regression analysis over the entire reference population was performed determining the risk of both SGA and IUGR by adjusting for maternal age, first delivery, maternal underweight status, pre-eclampsia, other treated thrombophilias or history of recurrent abortion.

Results: The SGA rates in the PS deficiency and control cohorts were 10.7% and 8.5%, respectively (p?>?0.05). There was no increased risk of SGA (unadjusted OR?=?1.28, 95% confidence interval [CI] 0.9–1.83; adjusted OR?=?1.35, 95% CI 0.91–2.01). The IUGR rate was 2.7% in pregnant women with PS deficiency versus 4.1% in the control group (p?>?0.05). Also, we did not find a significant risk of IUGR (OR?=?0.66; 95% CI 0.34–1.28; adjusted OR?=?0.843; 95% CI 0.42–1.70).

Conclusions: In women with PS deficiency treated with LMWH, the risk of SGA and IUGR is similar to the one found in healthy pregnant women.     

Adropin concentrations in term pregnancies with normal,restricted and increased fetal growth

Objective: To determine levels of adropin (implicated in insulin resistance and endothelial dysfunction) in intrauterine growth restricted (IUGR), large (LGA) and appropriate for gestational age (AGA) pregnancies.

Methods: Cord-blood (UC) adropin and insulin concentrations were measured in 30 IUGR, 30 LGA and 20 AGA full-term infants and their mothers (MS).

Results: No significant differences in adropin concentrations were observed between the three groups. In the IUGR group MS adropin was significantly decreased when neonates had higher birth weights [b?= ?0.003, 95% CI??0.006 to 0.0, p?=?0.043]. In all groups, MS adropin levels were positively correlated with UC ones (r?=?0.282, p?=?0.011) and were significantly increased in female neonates [b?=?0.977, 95% CI 0.122–1.832, p?=?0.026]. In the LGA group, MS insulin was negatively correlated with UC adropin (r?= ?0.362 p?=?0.049).

Conclusions: Increased maternal adropin levels in severe IUGR cases might represent a regulatory feedback mechanism against endothelial placental dysfunction. The positive correlation between maternal and umbilical cord adropin levels implies its transplacental transfer. Increased maternal adropin levels in female neonates could be attributed to interaction of adropin with fetal estrogens through vascular endothelial growth factor (VEGF). The negative correlation between maternal insulin and fetal adropin levels in the LGA group is probably attributed to their respective insulin resistance.     

Human papillomavirus infection and intrauterine growth restriction: a data-linkage study

Objective: Using unbiased population data, to examine whether having a positive Pap smear, and thus a high probability of Human Papilloma Virus (HPV) infection, is a significant risk factor for intrauterine growth restriction (IUGR) in a subsequent pregnancy.

Study design and methods: Two independent population-based databases, namely the South Australian Perinatal Statistics Collection and the South Australian Cervical Screening Database, were deidentified and linked by the SANT Datalinkage Service. Analyses were performed on cases where Pap smear screening data was available for up to 2 years prior to a singleton live birth. Population characteristics and pregnancy related data were compared statistically by normal birth weight versus IUGR (10th percentile – known as small for gestational age (SGA), small for gestational age) and (3rd percentile birth weight – known as VLBW, very low birth weight). The association between cervical screening results and IUGR was assessed using generalized linear log binomial regression models.

Results: A total of 31,827 women met the criteria. Of these, 1311 women (4.1%) had a positive Pap smear within 2 years of the current pregnancy. Those having a positive Pap smear were more likely to have a baby with IUGR than those with negative smear results. For SGA, 5.8% babies were from mothers with positive Pap smears compared to 4.0% with negative smears indicating a 40% higher risk of having an SGA baby (95%CI 20–70%) among women with positive Pap smears. For VLBW, 7.6% mothers had positive Pap smears compared with 4.0% with negative smears (p?Conclusions: Mothers with a positive Pap smear have an increased risk of IUGR, especially for VLBW, which is independent of other risk factors. The results confirm previous findings in a small study and emphasise the need to consider the risks of both cancer and IUGR in all HPV vaccination programs.     

Persistent pulmonary hypertension of the neonate and asymmetric growth restriction

Objective: To evaluate the possible associations between persistent pulmonary hypertension of the neonate, need for extra-corporeal membranous oxygenation, small for gestational age (SGA), and low ponderal index for gestational age in infants with persistent pulmonary hypertension of the neonate and in matched controls.Methods: Eighty-six infants with persistent pulmonary hypertension of the neonate delivered from 1991 to 1994 at our hospital were matched with 430 contemporaneous control singleton neonates. Birth weight and ponderal indices (100 x weight/length 3) less than the tenth percentile for gestational age and gender were defined as SGA and low ponderal index, respectively. We assessed associations between these markers, the presence of persistent pulmonary hypertension of the neonate, and the need for extracorporeal membranous oxygenation.Results: Low ponderal index was associated with persistent pulmonary hypertension of the neonate (odds ratio [OR] 5.4), whereas SGA was not. Low ponderal index (OR 4.0) was an independent correlate of persistent pulmonary hypertension of the neonate after adjustment with logistic regression for 5-minute Apgar scores less than 7, umbilical arterial pH less than 7.10, and presence of meconium. Low ponderal index was associated with need for extracorporeal membranous oxygenation in neonates with persistent pulmonary hypertension (P < .001).Conclusion: Fetal developmental events may significantly affect neonatal pulmonary status. Diminished neonatal nutritional status, as measured by low ponderal index for gestational age, is associated with increased risk of persistent pulmonary hypertension of the neonate and severity of the disease process.     

Auxological and metabolic study in small for gestational age children during 2 years follow-up

Objective.?To compare auxological and metabolic status of preterm (PT) and fullterm (FT) small for gestational age (SGA) babies from birth until age 2 years and to study the role of intrauterine growth retardation (IUGR) in auxological and metabolic outcome in SGA babies.

Methods.?We enrolled 44 SGA babies (22 FTs, 22 PTs) followed up six monthly. Anthropometric and metabolic measurements (fasting glucose, basal insulin level, total-cholesterol, triglycerides) were performed. HOMA-IR was selected to assess insulin sensitivity.

Results.?Both FTs and PTs from birth to age 6 months showed a significant increase in weight and length; the weight gain decreased from 6 to 12 months only in PTs. At 24 months, we observed catch-up growth in 90% of FTs and 87% of PTs. Insulinemia and HOMA-IR decreased from birth to 24 months, in particular between 6 and 12 months. PTs SGA with IUGR were significantly smaller than FTs SGA without IUGR (p?=?0.01) and showed a lower length growth velocity. Moreover they showed also higher insulin levels and HOMA-IR at birth; these values decreased at 12 and 24 months.

Conclusions.?Our study showed no significant difference between PTs and FTs SGA in auxological and metabolic parameters. However, prematurity with IUGR proved to be a significant factor that should be considered in the timing of auxological follow-up of SGA subjects.     

Comparison study between induced and spontaneous term and preterm births of small-for-gestational-age neonates.

OBJECTIVE: To compare perinatal and maternal outcome between induced and spontaneous small-for-gestational-age (SGA) neonates at term and preterm deliveries. STUDY DESIGN: A cross-sectional study was designed and two groups were identified at each gestational age: study group - SGA neonates born after induction of labor, comparison group - SGA neonates born after spontaneous onset of labor. SGA was decoded as birth weight below 10th percentile. The population consisted of 367 consecutive SGA singleton preterm neonates (24-36 weeks' gestation) and 3921 term SGA neonates (37-42 weeks' gestation) delivered between 1990 and 1997. Patients with antepartum death and congenital anomalies were excluded from this study. RESULTS: The prevalence of SGA neonates among preterm deliveries was significantly higher than among term deliveries (9.3 versus 6.1%, P<0.001). The rate of induction of labor among preterm SGA deliveries was significantly higher than term SGA deliveries (17.7 versus 13.4%, P=0.002). The rates hypertensive disorders, suspected IUGR, placental abruption, cesarean section, chorioamnionitis and endometritis were significantly higher among preterm SGA than in term SGA. A multiple logistic regression analysis demonstrated that suspected IUGR, severe PIH (but not mild PIH), chronic hypertension and placental abruption were independent risk factors for induction of labor among preterm SGA neonates. In addition to these factors, oligohydramnios was considered to be an independent risk factor only among term SGA. No significant differences were found in the mean birthweight and post-partum death rates between the induced and spontaneous preterm and term SGA. The incidence of Apgar score < 7 at 5 min was significantly lower only among induced term SGA. CONCLUSIONS: Induction of labor in preterm SGA neonates is performed mainly due to maternal severe hypertension disorders. The indications for induction of labor among term SGA include maternal hypertensive disorders (mild or severe) as well as neonatal status, represented mainly by oligohydramnios. In addition, induction of labor in preterm or term SGA neonates does not change neonatal outcome. Moreover, since no evidence of improved neonatal outcome was demonstrated in either indicated group, preterm or term, the question of timing and indications for induction of labor should be discussed.     

Preterm premature rupture of the membranes is associated with asymmetric intrauterine growth retardation and smaller placentas

Objective: To show that infants delivered prematurely because of preterm premature rupture of the membranes (PPROM) show a tendency for asymmetric intrauterine growth retardation (IUGR). At the same time, to demonstrate that these pregnancies exhibit nutritional deprivation by the presence of correspondingly smaller placentas, as demonstrated by the placental-fetal ratio.Study Design: A prospective study was performed over 2 years comparing the tendency for IUGR in infants born of pregnancies with PPROM (N = 86), as compared to normal term controls (N = 351). The tendency for growth restriction in the neonate was determined using the ponderal index at birth. Exclusion criteria included pregnancies complicated by diabetes, hypertension, preeclampsia, multiple gestations, genetic, and other recognized causes of IUGR. Four controls were selected for each study patient who delivered the same day. The mean ponderal index (PI_m) was compared, as were the mean placental-fetal weight ratios (PWt/PI)_m, for both groups. A comparison of the PI_m and (PWt/PI)_m for infants delivered prematurely with and without rupture of membranes was also noted. Analysis was by the paired Student’s t test and χ² test.Results: The newborn PI was found to be independent of maternal age, gravidy, and parity. The number of male and female infants were not significantly different in the control and study groups. The PI_m for the PPROM group (PI_m = 2.33, SD = 0.29) was significantly smaller than that for the controls (PI_m = 2.52, SD = 0.23) (P < .0005). Similarly the (PWt/PI)_m for the PPROM group (mean = 194.8, SD = 49.9) was significantly smaller than that for the control group (mean = 273.4, SD = 54.2) (P < .0005). Mean values of PI and PWt/PI for preterm deliveries with, as compared to without rupture of membranes, showed no significant differences.Conclusions: Using the ponderal index to detect IUGR, a significant association of IUGR is noted in infants delivered subsequent to PPROM. This growth impairment is accompanied by significantly smaller placentas.     

Maternal serum ferritin as a clinical tool at 34–36 weeks’ gestation for distinguishing subgroups of fetal growth restriction

Objective: To compare maternal ferritin levels across pregnancies with fetal growth restriction including SGA and IUGR compared to appropriate for gestational age (AGA). Methods: Three groups were enrolled: AGA, SGA (birth weight below 10th percentile for gestational age with no placental insufficiency findings), and IUGR (birth weight below 5th percentile for gestational age accompanied by abnormal umbilical artery Doppler waveforms and/or oligohydramnios). Maternal serum ferritin samples were obtained at gestational weeks 34 through 36, and delivery occurred at or beyond 36 weeks. Results: A total of 126 pregnancies with AGA (36%), SGA (40%), and IUGR (24%) were enrolled. The mean maternal serum ferritin level was higher in the IUGR group than in the AGA group (59?μg/l versus 32.5?μg/l, p?Conclusion: Maternal serum ferritin levels differ in pregnancies with IUGR. The role of maternal serum ferritin measurements as a clinical tool for distinguishing different forms of fetal growth restriction warrants further investigation.     

Long-term cardiovascular hospitalizations of small for gestational age (SGA) offspring born to women with and without gestational diabetes mellitus (GDM)‡

Abstract

Objective: To assess whether delivery of small for gestational age (SGA) neonates to mothers with gestational diabetes mellitus (GDM) increases the risk of long-term cardiovascular offspring hospitalizations compared to SGA neonates born to mothers without GDM. Study design: This is a population-based retrospective cohort study. The study group was SGA offspring born to mothers with GDM (n?=?259), while the control group was SGA offspring born to mothers without GDM (n?=?9053). The main factor evaluated was offspring cardiovascular hospitalizations up to the age of 18?years. Kaplan-Meier survival curve was used to estimate cumulative incidence of cardiovascular hospitalizations. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (HR) for cardiovascular hospitalizations. Results: SGA children born to mothers with GDM had significantly higher rates of cardiovascular-related hospitalizations (1.9% vs. 0.7%, p?=?.026). A Kaplan-Meier survival curve demonstrated that SGA children born to GDM mothers had a higher cumulative incidence of cardiovascular hospitalizations (log-rank p?=?.037). The Cox regression model, while controlling for confounders, demonstrated that delivery of SGA neonates to mothers with GDM is independently associated with long-term cardiovascular offspring hospitalizations (adjusted HR =2.6; 95% CI 1.02–6.55 p?=?.045). Conclusion: Delivery of SGA neonates born to mothers with GDM is independently associated with long-term cardiovascular offspring hospitalizations.     

Comparison of customized and cohort-based birthweight standards in identification of growth-restricted infants in GUSTO cohort study

Background: The aim was to evaluate the ability of customized and cohort birthweight standards in discriminating intrauterine growth retardation (IUGR).

Methods: Birthweights (BWs) of GUSTO singleton infants born at gestational age (GA) 35–41 weeks were converted using two standards: (a) GUSTO cohort-based BW centile adjusted for GA and baby gender; (b) customized BW percentile calculator adjusted for maternal height and weight, race, parity, GA and gender. Infants were classified into three groups: (1)?<?10th BW centile by customization– customized-SGA, (2)?<?10th BW centile by GUSTO– GUSTO-SGA; and (3)?>?10th BW centile by both standards – BOTH-non-SGA.

Results: Of the 1011 infant–mother dyads, 68 were customized-SGA and 104 were GUSTO-SGA, with concordance of 61% (n?= 63) for SGA. While 5 (7%) of customized-SGA were not SGA by GUSTO-charts, 41 (39%) of GUSTO-SGA were not SGA by customized-charts. Customized-SGA had significantly the least growth in abdominal circumference (AC) and highest head circumference (HC): AC growth ratio between second and third trimester; and the lowest mean BW, ponderal index and placental weight than other groups.

Conclusion: Customized-SGA standard was a better discriminator of pathologic fetal growth based on AC growth. It improved strength of association with pathology and in our population reduced false positives (41/104?=?39%) in the assessment of SGA.     

Long-term endocrine outcome of small for gestational age infants born to mothers with and without gestational diabetes mellitus

Abstract

Small for gestational age (SGA) infants and infants born to mothers with gestational diabetes mellitus (GDM) are at an increased risk for significant morbidity and mortality, mainly metabolic disorders. We aimed to question the long-term endocrine morbidity of SGA infants born to mothers with GDM compared to SGA infants born to non- diabetic mothers. A population-based cohort study was performed to assess the risk for endocrine morbidity among children born SGA to mothers with and without GDM. The main outcome evaluated was endocrine morbidity of the offspring up to the age of 18 years, predefined in a set of ICD-9 codes. Endocrine morbidity included thyroid disease, insulin and non-insulin dependent diabetes mellitus, hypoglycemia, childhood obesity, parathyroid hormone disease, adrenal disease, and sex hormone disease. All SGA infants born between the years 1991 and 2014 and discharged alive from the hospital were included in the study. Multiple pregnancies, infants with congenital malformations or chromosomal abnormalities and mothers lacking prenatal care were excluded from the analysis. Kaplan–Meier survival curve was constructed to compare cumulative endocrine morbidity. A Cox proportional hazards model was conducted to control for confounders. During the study period, 9312 newborn infants met the inclusion criteria, of them 259 SGA infants were born to mothers with GDM and 9053 SGA infants were born to mother without GDM. No significant differences in long-term endocrine morbidity were noted between the groups (0.8% in children born to mothers with GDM vs. 0.5% in children born to non-diabetic mothers, p?=?.62). Likewise, the Kaplan–Meier survival curve did not demonstrate a significantly higher cumulative incidence of endocrine morbidity in offspring of women with GDM (log rank test p=.67). In a Cox regression model, while controlling for ethnicity, hypertensive disorders, preterm birth, and maternal age, delivery of an SGA neonate to mother with GDM was not associated with long-term endocrine morbidity of the offspring (adjusted HR 1.2, 95% confidence interval 0.27–5.00, p=.82). SGA infants born to mothers with GDM are not at an increased risk for long-term endocrine morbidity as compared with SGA infants born to non-diabetic mothers.     

Serum fetuin-A/alpha2-HS-glycoprotein in human pregnancies with normal and restricted fetal growth

Objective. To investigate circulating concentrations of human fetuin-A (important fetal glycoprotein, involved in vascular pathology and bone metabolism) in mothers, fetuses and neonates from intrauterine-growth-restricted (IUGR, associated with low bone mass at birth and metabolic syndrome in adult life) and appropriate-for-gestational-age (AGA) pregnancies.

Methods. Serum fetuin-A concentrations were prospectively measured in 40 mothers, the doubly-clamped umbilical cords (representing fetal state) and their 20 IUGR and 20 AGA full-term neonates on postnatal day 1 (N1) and 4 (N4).

Results. No significant differences in fetuin-A concentrations were observed between groups, or between maternal, fetal and neonatal samples in both groups. In the AGA group, maternal fetuin-A concentrations positively correlated with fetal and N1 ones (r = 0.599, p = 0.005 and r = 0.469, p = 0.037, respectively). In the IUGR group, maternal fetuin-A concentrations positively correlated with N4 ones (r = 0.541, p = 0.014).

Conclusion. Serum fetuin-A concentrations do not differ between IUGR cases and AGA controls. Maternal and fetal fetuin-A concentrations are similar and positively correlated, indicating the likelihood of passive transplacental transfer of this substance.     

Impact of transient period of metabolic adaptation on perinatal asphyxia in neonates with intrauterine growth retardation

Introduction: Temperature, glycemia and respiration make neonatal energy triangle (NET). In growth retardation (IUGR) neonates pathological metabolic adaptation exists in transient neonatal period.

Aim: The of this study was to examine the occurrence of pathological NET and check its impact on perinatal asphyxia during the transient period in IUGR neonates.

Material and methods: One hundred and fifty-nine neonates with IUGR were classified into – early preterm, late preterm and term neonates. By the presence of hypothermia, hypoglycemia and hypoxia in the first hour after birth neonates were classified into: group of pathological NET, group of unstable NET and group of stable NET. We analyzed distribution per body mass, gestational age, type of IUGR, gender and the frequency of perinatal asphyxia between the groups.

Results: The late preterm neonates were the most frequent in the group of pathological NET. Perinatal asphyxia was diagnosed in 52 (32.7%) neonates, with highest frequency in the group of pathological NET. Univariate binary logistic regression analysis showed that pathological NET in neonates with IUGR is significant predictor for perinatal asphyxia occurrence (OR?=?8.57; CI?=?4.05–18.12; p?R²?=?0.27).

Conclusion: Poor metabolic adaptation in neonates with IUGR in the first hour after birth is significant risk factor for the perinatal asphyxia.     

Perinatal collagen turnover markers in intrauterine growth restriction

Objective: To investigate bone and connective tissue collagen turnover in intrauterine growth restricted (IUGR) pregnancies, by determining circulating markers of type I collagen synthesis (carboxy-terminal propeptide of type I procollagen [PICP], representing bone formation) and degradation (cross-linked telopeptide of type I collagen [ICTP], representing bone resorption) as well as type III collagen synthesis (N-terminal propeptide of type-III procollagen [PIIINP], reflecting growth and tissue maturity).Methods: Plasma PICP, ICTP and PIIINP concentrations were measured in 40 mothers and their 20 asymmetric IUGR and 20 appropriate for gestational age (AGA) full-term fetuses and neonates on postnatal day 1-(N1) and 4-(N4).Results: Fetal PICP, fetal and N4 ICTP, as well as fetal, N1 and N4 PIIINP concentrations were higher in the IUGR group (p?≤?0.038, in all cases). In both groups, maternal PICP, ICTP and PIIINP concentrations were lower than fetal, N1 and N4 ones (p?<?0.001, in each case).Conclusions: Type I collagen turnover is enhanced in IUGR than AGA fetuses/neonates. Similarly, fetal/neonatal PIIINP concentrations are elevated in IUGR, probably due to stress, responsible for induction of tissue maturation, and/or to impaired excretory renal function, leading to reduced protein clearance. Fetal/neonatal PICP, ICTP and PIIINP concentrations are higher than maternal concentrations, possibly reflecting increased skeletal growth and collagen turnover in the former.     

Optimising enteral nutrition in growth restricted extremely preterm neonates – a difficult proposition

Background: Optimising enteral nutrition of extremely preterm neonates (EP: Gestation <28 weeks) with intrauterine growth restriction (IUGR) has always been difficult considering their higher risk of necrotising enterocolitis (NEC), and frequency of feed intolerance.

Aim: To evaluate the nutritional outcomes in EP neonates with IUGR.

Methods: Data on demographic characteristics, feeding details (e.g. type of milk, postnatal age at start), and outcomes to discharge or death were collected from the medical notes for all EP neonates, who survived first 72?h of life, between January 2009 and December 2010. A standardised feeding protocol was followed during the study period.

Results: 38/220 (17.3%) EP neonates admitted during the study period had IUGR. The mean (IQR) age at start of minimal enteral nutrition [7 (5–10) versus 5 (4–8) days, p?=?0.005), and nutritional (1?ml/2hourly) feeds [12 (8–15) versus 9 (7–13) days, p?=?0.034] was significantly delayed in IUGR compared to non-IUGR neonates. IUGR neonates reached full enteral feeds (150?ml/kg/day) at a significantly late median (IQR) postnatal age [32 (21–40) versus 24 (17–31) days, p?=?0.009), taking longer time to achieve this milestone [20 (15–34) versus 16 (12–4) days, p?=?0.008). The incidence of postnatal growth restriction was significantly higher in IUGR versus non-IUGR (73% versus 45%, p?=?0.003) neonates. The incidence of?≥?Stage II NEC was low [18/220 (8.1%)] to make valid statistical comparisons.

Conclusion: Optimising enteral nutrition in growth restricted extremely preterm neonates is difficult using the current strategies for enteral nutrition.     

Limitations of ultrasound in diagnosing intrauterine growth restriction in severe preeclampsia

Objective.?The objective of this study was to determine test characteristics of ultrasound in detecting intrauterine growth restriction (IUGR) in severe preeclampsia (S-PEC).

Study design.?We performed a prospective study (2005–2007) to evaluate risk factors for PEC. Women with severe PEC and an ultrasound ≤3 weeks of delivery were enrolled. Chi square analysis determined associations between diagnosis of IUGR and small for gestational age (SGA) birth weight. Multivariable logistic regression was used to control for confounders. Fetal growth rate and test characteristics of ultrasound were calculated.

Results.?Ninety-three patients were enrolled. There was a significant association between IUGR and SGA, but no association between maternal demographic factors and IUGR. Test characteristics of ultrasound to diagnose IUGR in severe PEC were: sensitivity 56.7%, specificity 93.7%, PPV 81.0%, NPV 81.9%. The positive likelihood ratio (+LR) for ultrasound to detect IUGR in severe PEC was 8.9.

Conclusion.?Current ultrasound practice has moderately good positive and negative predictive values and a high specificity for the diagnosis of IUGR in women with severe PEC. However, the poor sensitivity and low + LR indicate that additional modalities are needed to improve the usefulness of ultrasound in detecting IUGR in severe PEC.     

Protein expression in the brain of rat offspring in relation to prenatal caloric restriction

Objective: Intrauterine growth restriction (IUGR) has been associated with decreased supply of crucial substrates to the fetus and affects its growth and development by temporarily or permanently modifying gene expression and function. However, not all neonates born by calorie restricted mothers are IUGR and there are no reports regarding their brain protein expression vis-à-vis that of their IUGR siblings. Here, we investigated the expression of key proteins that regulate growth and development of the brain in non-IUGR newborn pups versus IUGR siblings and control pups.

Methods: Rat brain proteins were isolated from each group upon delivery and separated by two-dimensional gel electrophoresis (2-DE).

Results: 14-3-3 Protein, calreticulin, elongation factor, alpha-enolase, fascin, heat-shock protein HSP90 and pyruvate kinase isozymes were significantly increased (p?<?0.05) in samples obtained from IUGR newborn pups compared to non-IUGR. Conversely, collapsin response mediator proteins, heat-shock70 and peroxiredoxin2 were decreased in IUGR group compared to non-IUGR.

Conclusions: In our experimental study, IUGR pups showed an altered proteomic profile compared to their non-IUGR siblings and non-IUGR controls. Thus, not all offspring of calorie-restricted mothers become IUGR with the accompanying alterations in the expression of proteins. The differentially expressed proteins could modulate alterations in the energy balance, plasticity and maturation of the brain.     

The association between birth weight at term and long-term endocrine morbidity of the offspring*

Objective: To investigate whether small-for-gestational-age (SGA) and large-for-gestational-age (LGA) birth weight at-term poses an increased risk for long-term pediatric endocrine morbidity.

Study design: A retrospective population-based cohort study compared the incidence of long-term pediatric hospitalizations due to endocrine morbidity of singleton children born SGA, appropriate-for-gestational-age (AGA), and LGA at-term. A multivariate generalized estimating equation (GEE) logistic regression model analysis was used to control for confounders.

Results: During the study period, 235,614 deliveries met the inclusion criteria; of which 4.7% were SGA (n?=?11,062), 91% were AGA (n?=?214,249), and 4.3% were LGA neonates (n?=?10,303). During the follow-up period, children born SGA or LGA at-term had a significantly higher rate of long-term endocrine morbidity. Using a multivariable GEE logistic regression model, controlling for confounders, being delivered SGA or LGA at-term was found to be an independent risk factor for long-term pediatric endocrine morbidity (Adjusted OR?=?1.4; 95%CI?=?1.1–1.8; p?=?.015 and aOR?=?1.4; 95%CI?=?1.1–1.8; p?=?.005, respectively). Specifically, LGA was found an independent risk factor for overweight and obesity (aOR?=?1.7; 95%CI?=?1.2–2.5; p?=?.001), while SGA was found an independent risk factor for childhood hypothyroidism (aOR?=?3.2; 95%CI?=?1.8–5.8; p?=?.001).

Conclusions: Birth weight either SGA or LGA at-term is an independent risk factor for long-term pediatric endocrine morbidity.