Renal function is impaired in small for gestational age premature infants

Objectives: Small for gestational age (SGA) premature infants are at increased risk for complications. We aimed to evaluate if SGA infants are at higher risk for presenting renal insufficiency in the newborn period compared to appropriate for gestational age (AGA) premature infants. Methods: We conducted a retrospective case-control study of infants ≤ 34 weeks gestation. Markers of renal function based upon the Acute Kidney Injury Network were compared between both groups. Results: Twenty SGA infants were compared to twenty AGA infants matching in sex and gestational age. SGA infants had higher serum creatinine on day of life (DOL) 1 (p = 0.014) and DOL 3 (p = 0.05) and a higher overall maximum creatinine concentration (p = 0.013). They were also more likely to have an increase in serum creatinine more than 0.3?mg/dL in a 48-h period (OR: 7.8, p = 0.008) and increase in serum creatinine more than 50% in a 48-h period (OR: 12.4, p = 0.002). Urine output (mL/kg/h) was significantly less in the SGA group on DOL 3 (p = 0.002) and DOL 7 (p = 0.017). Conclusions: SGA infants are at increased risk for renal insufficiency during the neonatal period, thereby implying the need for special considerations in their fluid and medication management.     

Pathology of placenta from small for gestational age infants

Pathologic study was carried out in 125 placentas, of which 25 were from cases of small for gestational age infants (SGA) and 100 from normal pregnancies. Ultrastructural study was done in 5 cases of each group. In the SGA group placenta circumvallata and velamentous insertion of cord were more frequently seen and the percentages of syncytial knots, cytotrophoblastic cells, and fibrinoid necrosis, stromal fibrosis and obliterative endarteritis of chorionic villi were also higher. Deficiency of vasculo-syncytial membranes and unduly thick trophoblastic basement membranes were common features of the SGA placentas. The most significant ultrastructural finding was the spasticity of capillaries of the villous stroma. It is believed that insufficient utero-placental blood flow may lead to the occurrence of SGA infants.     

Decreased cerebrovascular resistance in small for gestational age infants

Using a transcutaneous Doppler technique we found a significantly lower cerebrovascular resistance and higher cerebral blood flow velocity indicating vasodilatation and increase of cerebral blood flow in small for gestational age infants compared with appropriate for gestational age infants during the first days of life. We speculate that these findings are due to a continuation of the fetal situation in which chronic hypoxia, mostly caused by pregnancy-induced hypertension, possibly causes a prostacyclin-induced vasodilatation.     

Clinical outcome of small for gestational age preterm infants

Data from 55 preterm SGA infants and 55 preterm AGA infants matched for gestational age and sex were reviewed retrospectively. An increased incidence of perinatal hypoxia (30 vs. 18), gastrointestinal problems, minor infections (27 vs. 9), hematological problems and increased mortality (21.8% vs. 7.2%) was observed in the SGA infants. The incidence of HMD was higher in the AGA group (not significant), but the HMD was much more severe in the SGA group. Mortality as a result of HMD was significantly higher in the SGA group. The percentage of handicapped children is 19% in the SGA group and 9% in the AGA group. The percentages of severely handicapped children are 4.8% and 2.3% respectively. The combination of prematurity and severe intrauterine growth retardation in the SGA group caused a higher mortality and morbidity than was seen in their AGA controls. This clinical performance of SGA preterm infants is important especially for those who have to decide at what moment such a child should be delivered by caesarean section.     

Plasma adrenomedullin levels in pregnancies with appropriate for gestational age and small for gestational age infants.

AIMS: To evaluate whether maternal and fetal plasma adrenomedullin levels in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. METHODS: Maternal and fetal circulating adrenomedullin levels were compared between 62 pregnancies with AGA (43 delivered vaginally and 19 delivered by elective cesarean section) and 28 pregnancies with SGA (20 delivered vaginally and 8 delivered by elective cesarean section) at birth. Plasma adrenomedullin levels were measured from maternal and cord venous blood samples using a radioimmunoassay. Umbilical artery blood pH was also measured. RESULTS: There were no significant differences for maternal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. There were also no significant differences for fetal total adrenomedullin levels, mature adrenomedullin levels, and its ratio among the groups. In the AGA group delivered vaginally, fetal mature/total adrenomedullin ratio (mean +/- standard error, 16.6 +/- 0.7%) was significantly higher than the maternal ratio (13.8 +/- 0.6%) (p < 0.05). In the SGA group delivered vaginally, fetal mature/total adrenomedullin ratio (18.5 +/- 1.0%) was also significantly higher than the maternal ratio (14.5 +/- 0.6%) (p < 0.05). There was no significant difference in umbilical artery blood pH among the groups. CONCLUSIONS: These results suggest that maternal and fetal plasma circulating adrenomedullin levels may play a role in maternal and fetal cardiovascular adaptation during delivery in pregnancies with both AGA and SGA infants.     

Low maternal awareness of fetal movement is associated with small for gestational age infants

Our aim was to identify associations between information given to pregnant women about fetal activity, level of maternal awareness of fetal activity, maternal concern about decreased fetal movement, and pregnancy outcomes. This was a population-based cross-sectional study. Mothers with a singleton delivery were invited to answer an anonymous structured questionnaire before discharge from the delivery unit. Six hundred and ninety-one mothers participated (60.4% of eligible women). Women were highly aware of fetal activity. Yet, 25% did not receive any information from care providers about expected normal fetal activity. Receiving information about fetal activity was associated with increased maternal awareness (odds ratio, 2.0; 95% confidence interval [CI], 1.2-3.4). Low maternal awareness of fetal activity was associated with an increased risk of having a small for gestational age infant (odds ratio, 6.5; 95% CI, 3.5-12.3). Expectations about the normal frequency of fetal movements, as reported by the mothers, varied from 25 kicks/hour to 3 kicks/24 hours. Receiving information about expected fetal activity was associated with maternal concerns about decreased fetal movement, but not with improved outcomes. We conclude that receiving information about expected fetal activity was associated with maternal concerns, but not with improved outcomes.     

Neonatal outcomes of small for gestational age preterm infants in Canada

To compare the effect of small for gestational age (SGA) on mortality, major morbidity and resource utilization among singleton very preterm infants (<33 weeks gestation) admitted to neonatal intensive care units (NICUs) across Canada. Infants admitted to participating NICUs from 2003 to 2008 were divided into SGA (defined as birth weight <10th percentile for gestational age and sex) and non-small gestational age (non-SGA) groups. The risk-adjusted effects of SGA on neonatal outcomes and resource utilization were examined using multivariable analyses. SGA infants (n = 1249 from a cohort of 11,909) had a higher odds of mortality (adjusted odds ratio [AOR] 2.46; 95% confidence interval [CI], 1.93-3.14), necrotizing enterocolitis (AOR 1.57; 95% CI, 1.22-2.03), bronchopulmonary dysplasia (AOR 1.78; 95% CI, 1.48-2.13), and severe retinopathy of prematurity (AOR 2.34; 95% CI, 1.71-3.19). These infants also had lower odds of survival free of major morbidity (AOR 0.50; 95% CI, 0.43-0.58) and respiratory distress syndrome (AOR 0.79; 95% CI, 0.68-0.93). In addition, SGA infants had a more prolonged stay in the NICU, and longer use of ventilation continuous positive airway pressure, and supplemental oxygen (p < 0.01 for all). SGA infants had a higher risk of mortality, major morbidities, and higher resource utilization compared with non-SGA infants.     

Brainstem conduction time abnormalities in small for gestational age infants.

Brainstem auditory evoked responses (BAER) were recorded in 89 neonates born between 32 and 40 weeks, in order to analyze the consequences of intrauterine growth retardation on brainstem conduction time. The I-V interval was measured in 28 appropriate for gestational age (AGA) infants (control group), in 24 small for gestational age (SGA) infants with maternal hypertensive disease (MHD) and in 37 SGA infants without MHD. At any gestational age, SGA infants with MHD always presented an acceleration of their brainstem conduction time as compared to the other SGA infants. For the SGA full-term twins without MHD, the brainstem conduction time was delayed. These results reflect the specific consequences on brainstem development of the various factors responsible for intrauterine growth retardation (IURG).     

Comparison of late-second-trimester nonstress test characteristics between small for gestational age and appropriate for gestational age infants

OBJECTIVE: To compare electronic fetal heart rate (FHR) monitoring characteristics between appropriate for gestational age (AGA) fetuses and small for gestational age (SGA) fetuses and to determine whether SGA fetuses have specific abnormalities at second-trimester electronic fetal monitoring (EFM), using nonstress test. METHODS: Among 953 children born from 1993-1996, we identified 500 singleton infants born after 36 weeks' gestation of uncomplicated pregnancies in whom second-trimester (24-27 weeks' gestation) EFM records were obtained. Individual components of FHR patterns (baseline rate, baseline FHR variability, presence of acceleration [at least 10 beats per minute for at least 10 seconds], and periodic or episodic deceleration [at least 25 beats per minute for at least 15 seconds]) and birth characteristics were compared between AGA and SGA infants, or between pregnancies with or without second-trimester decelerations. RESULTS: Among 500 infants, 443 were AGA and 57 SGA; 105 had and 395 did not have second-trimester decelerations. Baseline FHR variability (12.9+/-3.2 beats per minute) in SGA fetuses was significantly higher than variability (10.3+/-3.4 beats per minute) in AGA fetuses (P<.001). Small for gestational age fetuses were significantly more likely to have second-trimester decelerations than AGA fetuses (33.3% vs. 19.4%, P<.05). There were no significant differences in baseline rate and accelerations between AGA and SGA infants. Small for gestational age infants were more frequent in pregnancies with second-trimester decelerations, compared with those without second-trimester decelerations (18.1% vs. 9.6%, P<.05). Baseline FHR variability in pregnancies with second-trimester decelerations was significantly higher than in pregnancies without second-trimester decelerations (12.2+/-3.7 vs. 10.0+/-3.1 beats per minute, P<.001). CONCLUSION: Periodic or episodic decelerations and increased FHR variability during late second-trimester EFM were associated with an increased risk of SGA birth weight.     

Population-based study on antenatal corticosteroid treatment in preterm small for gestational age and non-small for gestational age twin infants

Objectives: To assess the associations between antenatal corticosteroid use (ACU), mortality and severe morbidities in preterm, twin neonates and compare these between small for gestational age (SGA) and non-SGA twins.

Materials and methods: Population-based study using data collected by the Israel National Very Low Birth Weight infant database from 1995 to 2012, comprising twin infants of 24–31 weeks' gestation, without major malformations. Univariate and multivariable logistic regression analyses were performed.

Results: Among the 6195 study twin infants, 784 were SGA. Among SGA neonates, ACU were associated with decreased mortality (23.9% vs. 39.2%, p?p?=?0.0015), similar to the effect in non-SGA neonates (mortality 13.0% vs. 24.5%, p?p?P_interaction?=?0.69. Composite adverse outcome risk was also reduced in SGA (OR?=?0.78, 95% CI 0.50–1.23) and non-SGA groups (OR?=?0.78, 95% CI 0.65–0.95), P_interaction?=?0.95.

Conclusions: ACU should be considered in all mothers with twin gestation, at risk for preterm delivery at 24–31 weeks, in order to improve perinatal outcome.     

Methadone metabolism by early gestational age placentas

The objective of this study was to identify the enzyme that metabolizes methadone in preterm placentas. Microsomal fractions were obtained from preterm (17 to 34 weeks) placentas (36 total; 12 per each gestational age group) and their activity in metabolizing methadone to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was determined. The enzyme catalyzing the reaction was identified by using chemical inhibitors selective for various cytochrome P450 isozymes and monoclonal antibodies raised against them. The metabolism of methadone by microsomes revealed saturation kinetics. Methadone was N-demethylated to EDDP by aromatase. The affinity of methadone to aromatase (apparent Km) did not change with gestation, but the activity of the enzyme (Vmax) increased and varied widely between individual placentas. Aromatase/CYP19 is the placental enzyme metabolizing methadone during pregnancy. The variability in enzyme activity among individuals should be reflected by the concentration of methadone in the fetal circulation and might be one of the factors affecting the incidence and intensity of neonatal abstinence syndrome.     

Hyrtl's anastomosis, the only connection between the two umbilical arteries. A study in full term placentas from AGA infants with normal umbilical artery blood flow

BACKGROUND: The aim of this study was to describe the variable anatomy in the anastomosis between the umbilical arteries for better understanding of the physical characteristics of the umbilical flow velocity waveform (FVW). METHODS: The arterial system of 67 placentas from pregnancies with normal umbilical FVW and resulting in a full-term AGA infant was visualized by angiography. The method allowed study of the anatomy of the anastomosis between the umbilical arteries and calculation of the relative placental area supplied by each umbilical artery. RESULTS: In 60 cases there was one anastomosis between the umbilical arteries, in one case there were two, in four the anastomosis was absent, and another two cases had a single umbilical artery. The anastomosis was represented by a vessel, a fenestration or coalescence of the umbilical arteries. In case the anastomosis diameter was of at least that of the umbilical arteries, they supplied in mean 26% and 74% (+/- 8.2%) of the placental area respectively. When the anastomosis diameter was smaller than that of the umbilical arteries their supply areas were in mean 41% and 59% (+/- 6.0%) respectively. In placentas lacking anastomosis the two umbilical arteries supplied 45% and 55% (+/- 2.6%) respectively, indicating a higher degree of symmetry. CONCLUSIONS: By using angiography we were able to demonstrate the variable anatomy of the anastomosis of Hyrtl. We found the occurrence and width of the anastomosis was correlated to the symmetry in size between the supply areas of each umbilical artery.     

Maternal hypertension and neonatal outcome among small for gestational age infants

OBJECTIVE: To determine whether maternal hypertension might improve perinatal outcome among small for gestational age (SGA) infants (< 10th percentile). METHODS: Our prospective cohort comprised 17 Canadian neonatal intensive care units (NICUs) and 3,244 SGA singletons. Multivariable regression was used to analyze the relation between maternal hypertension and each of the following: SNAP-II (Score of Neonatal Acute Physiology; ordinal regression) and neonatal survival and survival without severe intraventricular hemorrhage (logistic regression), adjusting for potential confounders. RESULTS: There were 698 (21.5%) neonates born to hypertensive mothers. Inversely associated with lower SNAP-II scores (healthier infant) were antenatal steroids (complete course: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.54-0.83; incomplete: OR 0.71, 95% CI 0.56-0.88), lower gestational age (< 27 weeks: OR 0.06, 95% CI 0.05-0.08; 27-28 weeks: OR 0.11, 95% CI 0.07-0.17; 29-32 weeks: OR 0.28, 95% CI 0.23-0.35), 5-minute Apgar < 7 (OR 0.30, 95% CI 0.25-0.36), male gender (OR 0.80, 95% CI 0.70-0.92), and anomalies (OR 0.49, 95% CI 0.41-0.58). Maternal hypertension was associated with lower SNAP-II (healthier infant) (7.54 +/- 11.16 [hypertensive] versus 7.21 +/- 11.85 [normotensive]) on multivariable regression analysis (adjusted OR 1.25, 95% CI 1.05-1.49), as well as higher neonatal survival (93.0% versus 91.2%, and adjusted OR 1.9, 95% CI 1.2-3.0), but not survival without severe intraventricular hemorrhage (91.4% versus 87.0%, and adjusted OR 1.4, 95% CI 1.0-2.0), respectively. CONCLUSION: Among SGA neonates in NICU, maternal hypertension is associated with improved admission neonatal physiology and survival.     

Glycemic control in gestational diabetes mellitus--how tight is tight enough: small for gestational age versus large for gestational age?

The relationship between optimal levels of glycemic control and perinatal outcome was assessed in a prospective study of 334 gestational diabetic women and 334 subjects matched for control of obesity, race, and parity. All women with gestational diabetes mellitus were instructed in the use of a memory-based reflectance meter. They were treated with the same metabolic goal according to a predetermined protocol. Three groups were identified on the basis of mean blood glucose level throughout pregnancy (low, less than or equal to 86 mg/dl; mid, 87 to 104 mg/dl; and high, greater than or equal to 105 mg/dl). The low group had a significantly higher incidence of small-for-gestational-age infants (20%). In contrast, the incidence of large-for-gestational-age infants was 21-fold higher in the mean blood glucose category than in the low mean blood glucose category (24% vs. 1.4%, p less than 0.0001). An overall incidence of 11% small-for-gestational-age and 12% large-for-gestational-age infants was calculated for the control group. A significantly higher incidence of small-for-gestational-age infants (20% vs. 11%, p less than 0.001) was found between the control and the low category. In the high mean blood glucose category an approximate twofold increase was found in the incidence of large-for-gestational-age infants when compared with the control group (p less than 0.03). No significant difference was found between the control and mean blood glucose categories (87 to 104 mg/dl). Our data suggest that a relationship exists between level of glycemic control and neonatal weight. This information is helpful in targeting the level of glycemic control while optimizing pregnancy outcome in gestational diabetes comparable to the general population.     

Altered cord serum lipid levels associated with small for gestational age infants

OBJECTIVE: To determine whether small for gestational age (SGA) infants show changes in lipid metabolism that could distinguish growth-restricted subpopulations. METHODS: Sera from the arterial cord blood from 38 SGA infants were analyzed for apolipoprotein A-I level, total lipid content, and distribution of those lipids as triglycerides, diglycerides, free fatty acids, and phospholipids. Comparisons were made between appropriate for gestational age (AGA) controls (n = 25), SGA infants with a ponderal index below the tenth percentile (SGA I, n = 20), and SGA infants with a ponderal index above the tenth percentile (SGA II, n = 18). RESULTS: Total cord serum lipid content was markedly decreased in all SGA infants compared with AGA infants (2.8 times lower). Although SGA infants showed total lipid concentration decreases, SGA I and SGA II infants showed distinct characteristics. Infants in the SGA I group had higher triglyceride levels (1.8 times higher) and lower free fatty acid levels (1.4 times lower), compared with AGA infants (P < .001). The lipid subclass distribution in SGA II infants was not significantly different from that in AGA infants, with the exception of an increase in triglyceride concentrations (1.3 times higher). Although the 22-kD placenta-derived apolipoprotein A-I was similar in all groups, the level of fetal liver-derived 28-kD apolipoprotein A-I was 6.5 times lower in SGA I infants than in AGA or SGA II infants (P < .001). CONCLUSION: The SGA I infants appeared to have impaired utilization of circulating triglycerides, consistent with peripheral adipose depletion. Diminished fetus-derived apolipoprotein A-I levels with normal levels of placenta-derived apolipoprotein A-I levels might indicate a defect in the production or secretion of apolipoproteins associated with growth restriction.     

Low 1-hour glucose screens and small for gestational age infants.

OBJECTIVE: To determine whether a 1-hour glucose screen done at 26 to 29 weeks' gestation that is below the fifth percentile is predictive of having a small for gestational age (SGA) infant. STUDY DESIGN: Pregnancies with 1-hour glucose screens were analyzed retrospectively. A total of 600 cases had values below the fifth percentile (< 71 mg/dl). A total of 6784 controls had values between the 25th and 75th percentiles. Infants were classified as being SGA if they had birth weights less than the 10th percentile adjusted for gestational age and infant gender. The Student's t-test, Fisher's exact test, and logistic regression were used for statistical analysis. RESULTS: The incidence of SGA infants differed significantly between cases and controls, 16.2% versus 12.0% (p = 0.0043). This association remained significant after adjustment for race (p = 0.02). CONCLUSION: A 1-hour glucose screen with a result that is less than the fifth percentile is an independent risk factor for having an SGA infant.     

Neonatal screening for congenital cytomegalovirus infection in preterm and small for gestational age infants

Abstract

Congenital cytomegalovirus (CMV) infection affects many organs: reticuloendothelial and central nervous system are particularly involved. Congenital CMV infection is the leading cause of non-genetic sensorineural hearing loss. Hearing impairment can be present at birth or it can occur months or even years after birth. It is as well an important risk factor for antenatal stillbirth, preterm birth and small for gestational age (SGA) condition. For these reasons we should early identify congenital CMV infection investigating at least at risk newborns such as preterm or SGA babies given that a simple and standardized method for a large scale screening program is lacking. In our study, we found an association between congenital CMV infection and preterm births (3.03%) and with SGA condition (3.7%). Consequently, routine CMV urine detection should be performed at least in all babies born before 37 weeks of gestational age and in term SGA newborns.