Impact of delivery mode and gestational age on haematological parameters in Taiwanese preterm infants

Aim:   Reference ranges of haematological parameters in preterm infants are limited. The aim of this study is to determine the reference values of haematological parameters in preterm infants in Taiwan, and to assess the impact of gestational age and mode of delivery on these parameters.
Method:   Medical records were retrospectively reviewed in preterm infants admitted to National Taiwan University Hospital from January 2001 to December 2004. The inclusion criteria included infants with <37 weeks of gestation who had blood sampling within 24 h of birth. The exclusion criteria included those with maternal history of antepartum haemorrhage, chorioamnionitis, fever, sepsis, preeclampsia and hypertension; and perinatal history of twin-to-twin transfusion syndrome, feto-maternal transfusion, injury and infection.
Results:   Of 568 preterm infants with blood cell counts, 337 were available for analysis. There were trends of increase in red blood cell counts, haemoglobin levels and haematocrit values as gestation increased up to 34 weeks. In contrast, a trend of decrease was noted in mean corpuscular volume values. There was an initial trend of decrease in white blood cell counts and then increased after 31 weeks gestation. The platelet counts were essentially unchanged. Infants born by vaginal delivery generally had higher haematological parameters than those born by Caesarean section at different gestational ages except for mean corpuscular volume values.
Conclusions:   We established the reference ranges of haematological parameters in Taiwanese preterm infants. Health-care professionals must be cautious in clinical application of the haematological values because of varying antenatal and perinatal risk factors.     

EFFECT OF EARLY AND LATE CORD CLAMPING ON THE SYSTOLIC TIME INTERVALS OF THE NEWBORN INFANT

Abstract. The effect of early and late cord clamping on the left ventricular performance of the newborn infant was assessed by measuring the systolic time intervals from the indirect carotid pulse tracings and simultaneous phonocardiogram and electrocardiogram. The study was performed in 13 normal, full-term infants sequentially at 20–105 min, 6-6½ hrs, and 24–27 hrs of age. The umbilical cords were clamped early in 7 (E.C.) and clamped late in 6 infants (L.C.). The ratio of the pre-ejection period (PEP) to the left ventricular ejection time (LVET) was found to be significantly higher in the L.C. infants (mean±S.E., 0.400±0.18, 0.433±0.018, 0.410±0.021) compared with those of the E.C. (0.334±0.010, 0.347±0.009, 0.361±0.007) with p values of <0.01, <0.005 and <0.05, respectively in the three examination periods. This higher PEP/LVET ratios in the L.C. infants were mainly attributable to a prolongation of the PEP. It is suggested that late cord clamping, by allowing a sizable placental transfusion, appeared to affect adversely the left ventricular performance of the neonate. Furthermore, it is suggested that in evaluating systolic time intervals of the neonate during the first days of life, the volumic state or status of placental transfusion should be taken into consideration as a determinant.     

Admission of all gestations to a regional neonatal unit versus controls: Neonatal morbidity

Aims:   To describe the neonatal course and morbidity of all infants admitted to the regional neonatal intensive care unit (NICU) at Christchurch Women's Hospital (CWH) and to compare these with term control infants who were not admitted, in one calendar year. Infants in both NICU and control cohorts were enrolled in a 2-year follow-up study.
Methods:   All infants born over a 12-month period from February 2001 and admitted to the NICU, whose parents were domiciled in a defined geographical region, were eligible for study, together with every eighth healthy infant born at term and not admitted (to a total of 300). Comprehensive perinatal and neonatal data were collected for all enrolled infants.
Results:   A total of 387 NICU infants (86% eligible) were enrolled in the study together with 306 controls. Forty-one percent of NICU admissions were term and 40% were 33–36 weeks gestation. Term NICU infants were more likely to be born following induction of labour or by Caesarean section (34%, of which 50% were pre-labour) than control infants (18%, of which 32% were pre-labour). Infants of <28, 28–32, 33–36 and ≥37 weeks accounted for 74, 16, 7 and 3% of assisted ventilation days and 18, 31, 31 and 20% of total baby days, respectively.
Conclusions:   The need for assisted ventilation and length of NICU stay was inversely proportional to gestation. However, preterm infants of 28 weeks gestation and greater, as well as term infants, account for a high proportion of the NICU workload.     

A new wrinkle: Umbilical cord management (how,when, who)

In the past five years, umbilical cord management in both term and preterm infants has come full circle, going from the vast majority of infants receiving immediate cord clamping to virtually all governing organizations promoting placental transfusion, mainly in the form of delayed cord clamping (DCC). Placental transfusion refers to the transfer of more blood components to the infant during the first few minutes after birth. The different strategies for ensuring placental transfusion to the baby include delayed (deferred) cord clamping, milking of the attached cord before clamping, and milking of the cut cord. In this review, we address the current evidence to date for providing placental transfusion in different circumstances and the methods for implementation. We also highlight the gaps in knowledge and areas for future research.     

Effect of delayed cord clamping on iron stores in infants born to anemic mothers: a randomized controlled trial

OBJECTIVE:To study the effects of cord clamping on iron stores of infants born to anemic mothers at 3 months of age. DESIGN: Randomized controlled trial. SETTING: Teaching hospital. METHODS: Infants born to mothers with hemoglobin (Hb)<100 g/L were randomized at delivery to either immediate cord clamping (early group) or cord clamping delayed till descent of placenta into vagina (delayed group). The outcome measures were infant's hemoglobin and serum ferritin 3 months after delivery. RESULTS: There were 102 neonates randomized to early (n = 43) or delayed cord clamping (n = 59). The groups were comparable for maternal age, parity, weight and supplemental iron intake, infant s birth weight, gestation and sex. The mean infant ferritin and Hb at 3 months were significantly higher in the delayed clamping group (118.4 microg/L and 99 g/L) than in the early clamping group (73 microg/L and 88 g/L). The mean decrease in Hb (g/L) at 3 months adjusted for co-variates was significantly less in the delayed clamping group compared to the early clamping group (-1.09, 95% CI-1.58 to -0.62, p >0.001). The odds for anemia (<100 g/L) at 3 months was 7.7 (95% CI 1.84-34.9) times higher in the early compared to the delayed clamping group. CONCLUSION: Iron stores and Hb in infancy can be improved in neonates born to anemic mothers by delaying cord clamping at birth.     

Effect of Placental Transfusion on Iron Stores in Moderately Preterm Neonates of 30–33 weeks Gestation

Objective

To assess the effect of placental transfusion by delayed cord clamping (DCC) of 60 s or cord milking (CM) on serum ferritin levels at hospital discharge and 3 mo of postmenstrual age (PMA) in preterm neonates of 30 to 33 wk gestation in comparison to early cord clamping (ECC) within 10 s.

Methods

This mixed longitudinal study was conducted in moderately preterm neonates of 30 to 33 wk gestation born in a level III unit in Northern India with the study sample nested within a randomized controlled trial on placental transfusion. Intervention was delayed cord clamping for 60 s or cord milking compared with early cord clamping (within 10 s). Primary outcome measure was serum ferritin levels at discharge. Secondary outcome measures were serum ferritin levels at 3 mo PMA, incidence of anemia, need for blood transfusion and incidence of iron deficiency by 3 mo PMA.

Results

Out of the 215 randomly chosen infants, serum ferritin levels were estimated at least at one time point (at discharge or at 3 mo PMA) in 197 neonates [placental transfusion – 107; early cord clamping – 90]. Amongst them, ferritin level was estimated at discharge in 141 neonates, at 3 mo PMA in 76 neonates and at both time points in 20 neonates. Median (IQR) serum ferritin (μg/L) at discharge was significantly higher in placental transfusion group in comparison to the ECC group [399 (309,600) (n = 79) vs. 254 (190,311) (n = 62); p < 0.001]. Median (IQR) ferritin level at 3 mo PMA was not different between the study groups [20 (14,57) (n = 39) vs. 24 (8,52) (n = 37); p = 0.2]. The incidence of anemia by 3 mo PMA was significantly lesser in the placental transfusion group. No difference was observed in anemia requiring blood transfusion and iron deficiency by 3 mo PMA between the groups.

Conclusions

In 30 to 33 wk preterm neonates, placental transfusion resulted in significantly higher serum ferritin at discharge in comparison to early cord clamping. However, this benefit did not persist till 3 mo PMA.

     

PLACENTAL TRANSFUSION IN INFANTS OF DIABETIC MOTHERS ELUCIDATED BY PLACENTAL RESIDUAL BLOOD VOLUME

The influence of the method of delivery and the clamping technique on the placental transfusion is investigated by measurement of the placental residual blood volume in 58 infants of diabetic mothers and in 65 infants of nondiabetic mothers. It is shown that infants of diabetic mothers delivered vaginally compared with infants of diabetic mothers delivered by caesarean section, have a larger placental residual blood volume, if early clamping is employed. This relation suggests that also in infants of diabetic mothers, a temporary deposition of the distribution of the foeto-placental blood volume between the infant and the placenta occurs during vaginal delivery, because of the impaired venous backflow to the infant. The difference in the placental residual blood volume is more pronounced for infants of diabetic mothers than for infants of non-diabetic mothers. Further, it is shown that the placental residual blood volume is significant larger in infants of diabetic mothers but only after vaginal delivery with early clamping, compared with the same group of infants of non-diabetic mothers.     

Cord whole blood hyperviscosity: Measurement, definition, incidence and clinical features

Cord whole blood viscosity and haematocrit values (PCV) were determined in 2461 live birth infants. Viscosity measurements were performed on an Australian-designed coaxial narrow-gap viscometer. Normal viscosity values were determined for each week of gestation above 34 weeks. Hyperviscosity was defined as a viscosity value above 2 s.d. from the mean for each week of gestation and it occurred in 164 (6.7%) newborn infants. Although a close relationship existed between cord whole blood viscosity and PCV (r = 0.6597, P less than 0.0001), only 47.4% of polycythaemic infants (PCV greater than 65) were also hyperviscous and only 23.9% of hyperviscous infants were also polycythaemic. Hence, using the haematocrit to select which infants require viscosity studies fails to detect many hyperviscous newborn infants. Hyperviscosity was less common (3.6%, P less than 0.001) in infants who were born by Caesarean section and more common (16.5%, P less than 0.001) in those who were growth retarded. Of the hyperviscous infants, 84.5% were not growth retarded, most (87.8%) were term and most (86.6%) were delivered vaginally. Most hyperviscous newborn infants may thus remain undetected unless routine whole blood viscosity studies are performed.     

Autologous umbilical cord blood transfusion.

The purpose of this study was to examine some aspects of umbilical cord blood collection for autologous transfusion in premature infants. All 120 microbacterial cultures (aerobic and anaerobic) of cord blood samples as well as 30 cultures of mycoplasma were treated. Cord prothrombin fragment (F 1 + 2) concentrations were quantified at one and 10 minutes after clamping of the cord. F 1 + 2 concentrations assessed on 25 newborn infants were similar and no linear association with time of clamping could be drawn. This means that cord blood thrombosis is not activated for at least 10 minutes following clamping of the cord. As far as is known, the first newborn infant to benefit from this method of transfusion is reported here. The premature infant received two portions of autologous blood (on days 5 and 7). No untoward effects were noted. Blood, collected from the umbilical cord, is a safe source for autotransfusion, provided that bacteriological testing has been carried out.     

PLACENTAL TRANSFUSION IN THE PREMATURE INFANT WITH OBSERVATION ON CLINICAL COURSE AND OUTCOME

Blood volume was measured in 73 truly premature and 10 “small for date” term infants following early or late cord clamping at birth. Forty-five normal full term infants from a previous study were included for comparison. The results demonstrated that placental transfusion occurred if cord clamping was delayed. The amount of placental transfusion in terms of red cell volume per kg b.w. in the premature infants under 2001 g was less compared to that of both normal full term infants and premature infants above 2001 g. The clinical course showed high incidence and mortality from respiratory distress in premature infants under 2001 g. An interesting observation was the apparently higher mortality resulting from idiopathic respiratory distress syndrome in the late-clamped group weighing under 2001 g.     

Epigenetic modulation at birth – altered DNA-methylation in white blood cells after Caesarean section

Aim:  Delivery by C-section (CS) has been associated with increased risk for allergy, diabetes and leukaemia. Whereas the underlying cause is unknown, epigenetic change of the genome has been suggested as a candidate molecular mechanism for perinatal contributions to later disease risk. We hypothesized that mode of delivery affects epigenetic activity in newborn infants.
Methods:  A total of 37 newborn infants were included. Spontaneous vaginal delivery (VD) occurred in 21, and 16 infants were delivered by elective CS. Blood was sampled from the umbilical cord and 3–5 days after birth. DNA-methylation was analyzed in leucocytes.
Results:  Infants born by CS exhibited higher DNA-methylation in leucocytes compared with that of those born by VD (p < 0.001). After VD, newborn infants exhibited stable levels of DNA-methylation, as evidenced by comparing cord blood values with those 3–5 days after birth (p = 0.55). On postnatal days 3–5, DNA-methylation had decreased in the CS group (p = 0.01) and was no longer significantly different from that of VD (p = 0.10).
Conclusion:  DNA-methylation is higher in infants delivered by CS than in infants vaginally born. Although currently unknown how gene expression is affected, or whether epigenetic differences related to mode of delivery are long-lasting, our findings open a new area of clinical research with potentially important public health implications.     

Altered body composition in preterm infants at hospital discharge

Aim:  To test the hypotheses that body size is reduced and body composition altered in preterm infants at hospital discharge.
Methods:  Preterm infants (≤34 weeks gestation, ≤1750 g at birth) were enrolled. Body weight, length and head circumference were converted to standard deviation or z- scores. Body composition was measured using dual emission X-ray absorptiometry. The results were analysed using standard statistics.
Results:  One hundred and forty-nine infants (birth weight = 1406 ± 248 g, gestation = 31 ± 1.7 weeks) were studied. Postmenstrual age at discharge was 37 ± 1.2 weeks. Z -scores for head circumference, weight and length differed (−0.1 ± 0.6 > −1.4 ± 0.6 > −1.9 ± 0.6; p < 0.0001). Global fat-free mass was less in study infants than the reference infant at the same weight (2062 < 2252 g; p < 0.0001) or gestation (2062 < 2667 g; p < 0.0001). Global fat mass was greater in study infants than the reference infant at the same weight (307 > 198 g, 13 > 8%) or gestation (307 > 273 g; 13 > 9%; p < 0.0001). Changes in central fat mass closely paralleled those in global fat mass (r² = 0.76, p < 0.0001).
Conclusion:  Reduced linear growth and a reduced fat-free mass suggest that dietary protein needs were not met before discharge. A reduced fat-free mass coupled with an increased global and central fat mass echoes concerns about the development of insulin resistance and metabolic syndrome X in these high-risk infants.     

A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants

This study was carried out to assess the feasibility of late cord clamping of 45 s in preterm infants delivered mainly by caesarean section and the effects on post-partal adaptation and anaemia of prematurity. Prior to delivery, 40 infants of <33 gestational weeks were randomised to either 20 s or 45 s of late cord clamping. After the first shoulder was delivered, oxytocin was given intravenously to the mother in order to enhance placento-fetal transfusion while the infant was held below the level of the placenta. The 20 infants in group 1 (20 s) had a mean birth weight of 1070 g and a mean gestational age of 29 + 4/7 weeks versus 1190 g and 30 weeks in group 2 (45 s). On day 42 of life there were ten infants without transfusions in group 2 versus three in group 1 (P < 0.05). Out of the 20 infants in group 1, 19 and 15/19 in group 2 were delivered by caesarean section. There were no significant differences in Apgar scores, temperature on admission, heart rate, blood pressure and requirements for artificial ventilation. Conclusion Delayed cord clamping of 45 s is feasible and safe in preterm infants below 33 weeks of gestation. It is possible to perform the procedure at caesarean section deliveries and it should be performed whenever possible. It reduces the need for packed red cell transfusions during the first 6 weeks of life. Received: 10 February 2000 / Accepted: 12 April 2000     

Managing "healthy" late preterm infants

Background:  Late preterm infants are often managed in nursery rooms despite the risks associated with prematurity. The objective of this study was to determine the risks facing late preterm infants admitted to nursery rooms and to establish a management strategy.
Methods:  A total of 210 late preterm infants and 2648 mature infants were assessed. Infants born at 35 and 36 weeks' gestation weighing ≥2000 grams admitted to a nursery room and not requiring medical intervention at birth were of particular interest. The admission rates to the neonatal intensive care unit were evaluated according to the chart review.
Results:  Infants born at 35 and 36 weeks' gestation weighing ≥2000 grams had significantly higher admission rates than term infants at birth (Cochran–Mantel–Haenszel test, P < 0.001; common risk ratio, 4.27; 95% confidence interval, 2.41–7.55) and after birth ( P < 0.001; common risk ratio, 3.57; 95% confidence interval, 2.40–5.33). More than 80% of admissions from the nursery room to the neonatal intensive care unit after birth were due to apnea or hypoglycemia in neonates born at 35 and 36 weeks' gestation. The admission rates due to apnea increased with decreasing gestational age. The admission rates due to hypoglycemia with no cause other than prematurity accounted for 24.3% of admissions for those born at 35 weeks' gestation and 14.1% of admissions for those born at 36 weeks' gestation; hypoglycemia due to other causes accounted for fewer admissions.
Conclusion:  The management strategy for late preterm infants should be individualized, based on apnea and hypoglycemia. The respiratory state of late preterm infants should be monitored for at least 2 days, and they should be screened for hypoglycemia on postnatal day 0.     

Optimal timing of umbilical cord clamping for term and preterm babies

Deferring cord clamping allows blood flow between baby and placenta to continue for a few moments. This often leads to increased neonatal blood volume at birth. It also allows for longer transition to the neonatal circulation. Optimal timing for clamping the cord remains uncertain. This paper discusses the physiology of placental transfusion and presents the evidence from systematic reviews of randomised trials comparing alternative strategies for cord clamping for both term and preterm births.     

Sudden infant death syndrome: Effect of breast and formula feeding on frontal cortex and brainstem lipid composition

Methodology: Docosahexaenoic acid levels were measured by gas chromatography in samples of frontal lobe and brain-stem taken from 28 and 26 infants, respectively, who had died of sudden infant death syndrome (SIDS).
Results: Significantly higher levels of docosahexaenoic acid were present in the frontal lobe tissues derived from the 13 breast fed infants (age range = 3.3–36.3 weeks; mean 15.9 ± 11.3 weeks) compared to the 15 formula fed infants (age range = 6.9–47.7 weeks; mean 19.3 ± 10.6 weeks); mean (± s.d.) levels were 8.5 ± 1.1% and 7.6 ± 0.8% of total fatty acids ( P = 0.019). There was, however, no significant difference in brainstem docosahexaenoic acid levels between breast and formula fed infants.
Conclusions: Given these variable findings, further investigation of the relationship between dietary fatty acid intake and cerebral lipid levels may help to clarify whether different modes of feeding have a role in the pathogenesis of SIDS.     

Incidence of apnoea and bradycardia in preterm infants following DTPw and Hib immunization: A prospective study

Objective: To evaluate the incidence and severity of apnoea and bradycardia in hospitalized preterm infants following immunization at 2 months of age, and identify risk factors.
Methodology: A prospective study of 98 preterm infants, of gestational age 24–31 weeks, immunized at approximately 2 months post natal age with diphtheria-tetanus-whole cell pertussis vaccine (DTP_w) in the neonatal intensive care unit (NICU) at King George V Hospital Sydney. Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnoea and bradycardia in the 24 h periods pre- and post immunization.
Results: Only one infant had apnoea and/or bradycardia pre-immunization compared with 17 post immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation <90%). However, for five infants (30%) these events were associated with oxygen desaturation and two of these infants required supplemental oxygen. The group that had apnoea and/or bradycardia and the group that did not were not significantly different in terms of gestational age, birth weight and other variables. Infants who received Hib together with DTP_w were less likely to have apnoea and/or bradycardia than those given DTP_w alone.
Conclusion: When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnoea and bradycardia. We recommend that the cardio-respiratory function of hospitalized infants born at less than 31 weeks gestation be monitored for 48 h post immunization.     

Early versus late cord clamping: effects on peripheral blood flow and cardiac function in term infants

BACKGROUND: In the debate on the best cord clamping time in newborn infants, we hypothesized that late cord clamping enables an increased volemia due to blood transfer to the newborn from the placenta. AIM: To assess whether clamping time can affect limb perfusion and heart hemodynamics in a group of 22 healthy term newborn infants. STUDY DESIGN: A case-control study. SUBJECTS: Eleven early-clamped (at 30 s) vaginally-delivered newborn infants were compared with eleven late-clamped (at 4 min) newborns. OUTCOME MEASURES: The two groups were studied using near-infrared spectroscopy and M-mode echocardiography. RESULTS: Late cord clamping coincided with a higher hematocrit (median 62% versus 54%) and hemoglobin concentration (median 17.2 versus 15 g/dL), whilst there were no changes in bilirubin level. Echocardiography showed a larger end-diastolic left ventricle diameter (1.7 cm median value versus 1.5) coupled with unvaried shortening and ejection fraction values. There were no changes in calf blood flow, oxygen delivery, oxygen consumption or fractional oxygen extraction calculated from the NIRS measurements, or in foot perfusion index. CONCLUSIONS: Our results demonstrated that late cord clamping coincides with an increased placental transfusion, expressed by higher hematocrit and hemoglobin values, and larger left ventricle diameter at the end of the diastole, with no changes in peripheral perfusion or oxygen metabolism.     

Erythropoietin and hypoxia inducible factor-1 expression in the mid-trimester human fetus

Aim : Infants born prematurely lack a normal response to anemia and fail to increase erythropoietin (Epo) production despite an apparent need for improved tissue oxygenation. This anemia may involve a deficiency in the fetal and premature kidney to produce Epo. To evaluate fetal Epo production, Epo and hypoxia inducible factor-1 (HIF) mRNA expression was measured in the mid-trimester human fetus. Methods : Fetal liver and kidney samples were obtained at 11–22 wk of gestation. RNA was isolated and reverse transcribed from snap-frozen specimens. Epo and HIF cDNA concentrations were determined using real-time polymerase chain reaction (PRISM). Epo cDNA concentrations were standardized to HIF concentrations present in each sample. Results : HIF concentrations remained constant during gestation in kidney and liver samples. Epo cDNA concentrations in kidney did not change from 12 to 22 wk (8.4 ± 3.4 fg Epo pg⁻¹ HIF cDNA, 4.8 ± 1.4, 2.6 ± 0.4, and 4.2 ± 1.8 at 11–14, 15–16, 17–19, and 20–22 wk of gestation, respectively), while Epo cDNA concentrations in liver increased with gestation (74.5 ± 31.9 fg pg⁻¹ HIF, 23.8 ± 6.5, 96.4 ± 19.2 and 276.1 ± 28.5 at 12–14, 15–16, 17–19 and 20–22 wk of gestation, respectively, p ± 0.05, 20–22 wk of gestation liver samples vs all other gestations). Concentrations were 5–20-fold higher in liver than in kidney in each gestational group ( p ± 0.01, liver vs kidney).
Conclusion : HIF concentrations did not change with gestation in liver or kidney. The human fetal kidney produced approximately 5% of the total Epo mRNA measured during the second trimester. It remains to be determined how Epo production by these tissues is affected by premature birth.     

When to transfuse preterm babies

The physiological anaemia experienced by preterm babies is exacerbated by common care practices such as early clamping of the umbilical cord at birth and gradual exsanguination by phlebotomy for laboratory monitoring. The need for subsequent transfusion with red blood cells can be reduced by delaying cord clamping for 30-60 s in infants who do not require immediate resuscitation. The need for transfusions can be further reduced by limiting phlebotomy losses, providing good nutrition, and using standard guidelines for transfusion based on haemoglobin or haematocrit. What those guidelines should be is not clear. Analysis of two recent large clinical trials comparing restrictive and liberal transfusion guidelines leads to several conclusions. Restrictive transfusion guidelines may reduce the number of transfusions given, but there is no reduction in donor exposures if a single-donor transfusion programme is used. There is some evidence that more liberal transfusion guidelines may help to prevent brain injury, but information on the impact of transfusion practice on long-term outcome is lacking. Until further guidance emerges, transfusion thresholds lower than those used in the two trials should not be used, as there is no evidence that lower thresholds are safe.