Intrauterine growth restriction in a low-income country: Risk factors, adverse perinatal outcomes and correlation with current WHO Multicenter Growth Reference

Objective

To determine risk factors and adverse perinatal outcomes including nutritional status in the first week of life for newborns with intrauterine growth restriction-low birth weight (IUGR-LBW) in settings lacking facilities for routine intrauterine growth monitoring.

Methods

A cross-sectional study of all infants in an inner-city hospital in Lagos, Nigeria. IUGR-LBW was defined as full-term (gestational age ≥ 37 weeks) infant with low birth weight (< 2500 g). Nutritional/growth status at enrolment was determined by z-scores for length-for-age (HAZ), head circumference-for-age (HCZ), weight-for-age (WAZ) and weight-for-length (WHZ) based on current World Health Organization's Multicentre Growth Reference (WHO-MGR). Factors and adverse outcomes associated with IUGR-LBW were explored with multivariable logistic regression analyses.

Results

Some 145 (4.3%) infants were IUGR-LBW out of 2619 eligible singletons enlisted for this study. IUGR-LBW was significantly associated with teenage mothers (OR:2.90, 95% CI:1.22-6.89), lack of antenatal care (OR:1.88, 95% CI:1.33-2.65) and female gender (OR:1.38, 95% CI: 0.98-1.93; p = 0.062). The incidence of adverse outcomes across gestational age showed significant linear trend only for low five-minute Apgar scores (p = 0.024) and WAZ (p = 0.065). IUGR-LBW was associated with poor nutritional status across all four indices (p < 0.001) as well as low 5-minute Apgar scores (p = 0.095), sepsis (p = 0.053), hyperbilirubinemia (p < 0.001) and admission into special care baby unit (p = 0.009) after multivariable logistic regression analyses.

Conclusions

IUGR-LBW correlates with poor nutritional status in the first week of life based on WHO-MGR and affected infants can be detected early for effective surveillance in resource-poor settings. Improved prenatal care among teenage mothers is necessary for reducing IUGR-LBW burden.     

Pre-pregnancy iron reserves, iron supplementation during pregnancy, and birth weight

Background

Early iron supplementation in women with sufficient reserves could provoke iron excess resulting in haemoconcentration and low infant birth weight (IBW).

Aim

To clarify the influence of early iron supplementation on maternal iron status and the IBW, taking into account pre-pregnancy iron deposits.

Study design

Longitudinal, prospective study.

Subjects

Healthy women volunteers (n = 82) intending to become pregnant.

Outcome measures

Women were grouped as a function of their pre-pregnancy (low or present) iron stores (serum ferritin (SF) < or ≥ 20 μg/L) and time of commencement of iron supplementation during pregnancy; “early” (< 20 weeks) or “late” (≥ 20 weeks). Obstetric and clinical history, smoking habit, dietary intake and iron biochemical parameters were obtained at pre-pregnancy as well as at 1st, 2nd and 3rd trimesters. Haemoglobin, MCV, SF and transferrin saturation (TS) were measured.

Results

Overall, 36% of the women had low iron stores at pre-pregnancy. The mean early supplementation with iron was 140.7 mg/d and the mean of late supplementation was 99.01 mg/d. Early supplementation improves the biochemical status of the mother and does not provoke a significant increase in haemoconcentration relative to late supplementation independently of the pre-pregnancy iron levels.Supplemental iron had a positive effect on birth weight among women with pre-pregnancy low iron stores (β = 4.37; SE = 1.8; p = 0.038) and did not affect birth weight among women with present iron stores (β = − 0.008; SE = 3.03; p = 0.998).

Conclusion

Early iron supplementation with doses ~ 100 mg/d improves the biochemical status of the mother independently of her pre-pregnancy iron status. Supplementation with iron improves newborn birth weight in those women who start pregnancy with iron deficiency, and makes no significant difference to those women who are not iron deficient.     

Are former late-preterm children at risk for child vulnerability and overprotection?

Background

Parent perception of child vulnerability (PPCV) and parent overprotection (POP) are believed to have serious implications for age appropriate cognitive and psychosocial development in very low birth weight preterm children.

Aim

With recent concerns about suboptimal developmental outcomes in late-preterm children, this study was aimed at examining the relationship between history of late-preterm birth (34-36 6/7 weeks gestation), and PPCV, POP, and healthcare utilization (HCU).

Study design

This was a cross-sectional observational design.

Participants

Study participants were mothers of 54 healthy singleton children recruited from community centers including Women and Children Clinics (WIC), primary care clinics and daycare centers in the upper Midwest region.

Outcome measures

Outcome measures included Forsyth Child Vulnerability Scale (CVS), Thomasgard Parent Protection Scale (PPS) scores, and healthcare utilization (HCU). Potential covariates included history of life-threatening illness, child and maternal demographics, and maternal stress and depression using the Center for Epidemiologic Studies Depression Scale (CESD).

Results

HCU (p = 0.02) and the PPS subscales of supervision (p = 0.003) and separation (p = 0.03) were significant predictors of PPCV in mothers of 3-8years old children with late-preterm history. Age of the child (p = 0.008) and CVS scores (p = 0.005) were significant predictors of POP. Maternal age (p = 0.04), stress (p = 0.04), and CVS scores (p = 0.003) were significant predictors of HCU. Dependence, a subscale of the PPS, correlated with the child's age and gender even after controlling for age.

Conclusion

History of late-preterm did not predict MPCV, MOP, or HCU in healthy children. Future research is needed in larger more diverse samples to better understand causal relationships and develop strategies to lessen risks of MPCV and MOP.     

Prevention of deformational plagiocephaly in neonates

Background

Since the early 90s a striking rise in deformational plagiocephaly (DP) has been reported, and a causal link between the “back to sleep” position recommended to reduce the risk of sudden infant death syndrome. Recent data suggested that supine position is a risk factor only when combined with other environmental factors

Objective

To evaluate the impact of early intervention in the newborn environment on the prevalence of DP at 4 months of life.

Methods

A multicentric, prospective, controlled study in healthy term neonates. Within 72 h of birth, all parents received the usual recommendations for positioning their infants to prevent sudden infant death syndrome. In the Intervention group, recommendations were also given to encourage spontaneous and unhindered physical movement. At 1, 2 and 4 months, we looked for plagiocephaly and collected information on the infants' environment.

Results

The environment of the Intervention group (n = 88) was significantly more favorable to unhindered movement than in the control group (n = 51) (lower immobility score, p < 0.01). The prevalence of DP was significantly lower in the Intervention group than in the control group (13% vs. 31%, p < 0.001). For each supplementary hour of immobility during the third and fourth months of life, the risk of DP at four months doubled (OR:2.1[1.4-3.2]).

Conclusion

Early postnatal intervention on the maternity ward reduces the prevalence of DP. The recent rise in the incidence of DP could be related to a lack of stimulation and encouragement to physical movement rather than to supine positioning proposed for prevention of sudden infant death syndrome.     

Cardiovascular and metabolic outcome in 6-8 year old offspring of women with type 1 diabetes with near-optimal glycaemic control during pregnancy

Background

High maternal glucose concentrations during diabetic pregnancy may lead to health problems in the offspring later in life. We showed in a previous nationwide study on pregnancy outcome in type 1 diabetic women that prepregnancy care was good and a near-optimal glycaemic control during pregnancy was achieved (mean HbA1c 6.2%).

Aims

We investigated to what extent current care and treatment of pregnant women with type 1 diabetes were related to cardiovascular and metabolic disturbances in the offspring at school age. Additionally, we studied the influence of level of maternal glycaemic control, preterm birth and neonatal macrosomia (birth weight > p90).

Study design

Observational cohort study.

Subjects

6-8 year old offspring of women with type 1 diabetes (ODM, n = 213) and a control group of children of non-diabetic women (n = 79).

Outcome measures

BMI, blood pressure, parameters of fasting glucose regulation and lipid metabolism, components of the metabolic syndrome (overweight, hypertension, impaired fasting glucose, dyslipidaemia).

Results

Parameters of fasting glucose regulation and lipid metabolism and the frequency of components of the metabolic syndrome did not significantly differ between ODM and controls. Systolic blood pressure was slightly higher in ODM. The influence of level of maternal glycaemic control, preterm birth and neonatal macrosomia on outcome in ODM was limited.

Conclusions

Current care and treatment of pregnant women with type 1 diabetes result in cardiovascular and metabolic outcome in the offspring at 6-8 years of age that is comparable to that in children of non-diabetic women. Further follow-up should substantiate these results at later age.     

Episodes of hypocarbia and early-onset sepsis are risk factors for cystic periventricular leukomalacia in the preterm infant

Background

Septic episodes in preterm infants recently have been reported to be associated with periventricular leukomalacia (PVL). The role of hypocarbia as an independent risk factor for PVL in clinical studies raises many questions without conclusive answers.

Aims

To evaluate risk factors for cystic PVL focussing on the influence of hypocarbia.

Study design

Retrospective single centre case-control study.

Subjects

Preterm infants 24 to 35 weeks of gestational age and matched (1:2 for gender, birth year, gestational age and birth weight) controls.

Outcome measures

Multivariate analysis of perinatal factors being associated with cystic PVL diagnosed by serial ultrasound examinations.

Results

Univariate analysis of risk factors revealed lower 5 and 10 min Apgar scores, and higher rates of neonatal seizures, early-onset sepsis, neonatal steroids, respiratory distress syndrome with surfactant replacement therapy, and episodes of hypocarbia significantly being associated with PVL. Multivariate analysis using a logistic regression model revealed early-onset sepsis and hypocarbia being significantly associated with PVL (p = .022 and .024, respectively). Lowest PaCO₂ values did not differ as did not the duration of hypocarbia, but the onset of hypocarbia was significantly later in PVL cases compared to controls (mean 26 vs. 15 h, p = .033). Neurodevelopmental follow-up at a median time of 46 months was poor showing 88% of the cases having an adverse neurological outcome.

Conclusion

We found early-onset sepsis and episodes of hypocarbia within the first days of life being independently associated with PVL.     

Assessment of risk factors for survival of neonates born after second-trimester PPROM

Objective

Assess fetal risk factors which impact survival of infants delivered after second-trimester PPROM.

Study design

Clinical records of 87 patients, who all had second-trimester rupture of membranes between 14 + 0 and 24 + 6 weeks of gestation treated January 1998 to July 2005 were reviewed regarding perinatal outcome. This study is based on 25 surviving infants.

Results

13 of these 25 infants died in the hospital. Survivors had a higher birth weight (p = 0.008) and higher Apgar scores after 5 min (p = 0.005) than those infants dying. No differences in UA pH, the need of catecholamines and no association between histological verified chorioamnionitis and early onset sepsis were seen between survivors and nonsurvivors.

Conclusion

Higher gestational age at birth, higher birth weight, the absence of histologically verified chorioamnionitis and 5 min Apgar scores of ≥ than 6 have positive prognostic value for survival of neonates delivered preterm after second-trimester PPROM.     

Sepsis-associated electroencephalographic changes in extremely low gestational age neonates

Background

Sepsis in premature infants is associated with adverse neurodevelopmental outcomes. No previous studies have assessed acute changes in brain function during sepsis that might precede these adverse outcomes.

Methods

We performed amplitude-integrated electroencephalography (aEEG) monthly, from 28 weeks until 36 weeks of postmenstrual age, on 108 premature infants born before 28 weeks of gestation. Additional aEEG recordings were performed during infants' first episode of sepsis. Two independent readers who were blinded to the infant's gestational age at birth and chronologic age, as well as to whether the infant had sepsis, evaluated aEEG recordings for the presence of burst suppression and assigned a maturation score.

Results

Burst supression was found in 22% of aEEG recordings from infants without sepsis and 57% of recordings from infants with sepsis at the time of the recording (odds ratio = 4.2; 95% confidence limits = 2.4, 7.2; p < 0.001). After adjustment for postmenstrual age at the time of the recording, the association between sepsis and burst suppression persisted (odds ratio = 2.4; 95% confidence limits = 1.2, 4.8; p = 0.01). No statistically significant difference was found in the rate of increase in aEEG maturation score between infants with sepsis and those without.

Conclusion

Sepsis is associated with acute electroencephalographic changes, as indicated by burst supression, but not with a decreased rate of brain wave maturation.     

Effects of smoking during pregnancy on the optic nerve neurodevelopment

Background

Tobacco smoking during pregnancy alters neurodevelopment. Optical coherence tomography (OCT) provides precise measurements of the retinal nerve fiber layer (RNFL), which forms part of the central nervous system.

Aims

To assess using the OCT how smoking during pregnancy would affect optic nerve development as detected in human offspring.

Study design

Visual examination and OCT were performed on a group of children (n = 70; 4.15-13.50 years of age), classified as being exposed or not to maternal smoking during gestational period. The association between smoking during pregnancy and RNFL thickness was assessed by a linear regression analysis adjusted for possible confounding factors.

Results

Although visual outcomes did not differ between groups, a significant decrease in the RNFL thickness was found in the group of infants exposed to smoke (105.3 vs 95.6; p = 0.002), even when adjusting for gestational age, birth weight or gender.

Conclusions

OCT measurements show that intrautero exposure to tobacco smoke interferes with the development of the optic nerve.     

The effect of Lactobacillus rhamnosus GG supplemented enteral feeding on the microbiotic flora of preterm infants-double blinded randomized control trial

Background and Aim

Intestinal flora of preterms, dominantly presents with decreased amounts of physiological microbiota. This double blinded randomized control trial compared the stool of bottle fed preterms, randomized to receive lactobacillus rhamnosus GG (LGG) 6x109or placebo with formula feeding.

Study design

46 enterally fed preterms were randomized to receive probiotics or placebo within 0-3 days after birth. All personnel were blinded to treatment assignment. Faecal sampling was preformed at day 7, 21, 42. Presence of LGG colonization, somatic growth and length of hospital stay were recorded.

Results

60 patients were initially identified and enrolled but after exclusion criteria were applied, 21 babies were analyzed in the probiotic group and 26 in the placebo group. The number of lactobacillus were significantly higher (p = 0.014) on day 7, and 21 (p = 0.024) in the study group, and so was the number of enterobacteriaceae on all study days (p = 0.004, p = 0.000, p = 0.000), and Enterococcus sp on day 21 (p = 0.000). The amount of samples positive for staphylococci was significantly higher in the study group, on days 7 and 42 (p = 0.001 and 0.011). We did not show a significant difference in weight gain upon discharge between the groups p = 0.567, 95% CI (− 168; 305) or mean of hospital stay p = 0.421 95% CI (− 13.43;5.71).

Conclusions

A preterm infant formula with an addition of probiotics leads to a rapid growth of LGG in the gut of bottle fed infants, but does not decrease the amount of pathogenic organisms, nor increase weight gain during enteral feeding, or decrease length of hospital stay.     

Myocardial function in offspring 5-8years after pregnancy complicated by preeclampsia

Introduction

Preeclampsia and diabetic pregnancies share pathophysiological features suggested to influence epigenetic changes during foetal life with importance for later development and metabolic and cardiovascular diseases.

Aim

Our objective was to study the myocardium in offspring after pregnancy complications.

Methods

Forty-five children (age 5-8 years) delivered from pregnancies complicated by preeclampsia (n = 25), diabetes mellitus type 1 (n = 8) or gestational diabetes mellitus (n = 12) were included. Fifteen children from uneventful pregnancies served as controls. Myocardial functions of right and left ventricle were examined by conventional Doppler and tissue Doppler imaging (TDI).

Results

No major differences were found in the myocardial function between offspring of pregnancy complications and control group. However, the preeclampsia group had smaller hearts, increased heart rate and increased late diastolic velocity (A′-wave) at mitral valve attachments shown by both pulsed wave and colour TDI compared to the control and diabetic groups together (p ≤ 0.01).

Conclusion

Children born after preeclampsia may show effects of a negative impact on the heart already at the age of 5 to 8 years. The numbers of examined children were, however, limited.     

Placental pathology is associated with illness severity in preterm infants in the first twenty-four hours after birth

Background

Placental pathology is associated with long-term neurological morbidity. Little is known about the association of placental pathology and illness severity directly after birth in preterm infants.

Objective

To determine the association between placental pathology and illness severity in preterm infants during the first 24 h after birth.

Study design

Placentas of 40 preterm infants, born after singleton pregnancies (gestational age 25.4-31.7 weeks, birth weight 560-2250 g) were assessed for histopathology. Illness severity was measured using the Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE). A high SNAPPE reflects high illness severity.

Results

Examination of the 40 placentas revealed: pathology consistent with maternal vascular underperfusion (MVU) (n = 24), ascending intrauterine infection (AIUI) (n = 17), villitis of unknown aetiology (VUE) (n = 6), foetal thrombotic vasculopathy (FTV) (n = 6), elevated nucleated red blood cells (NRBCs) (n = 6), and chronic deciduitis (n = 10). SNAPPE ranged from 1 to 53 (median 10). Infants with elevated NRBCs had a higher SNAPPE than infants without elevated NRBCs (median 30 vs. 10, p = 0.014). The same was found for the presence of FTV (median 30 vs. 10, p = 0.019). No relation existed between SNAPPE and the other placental pathologies.

Conclusions

Elevated NRBCs and FTV were associated with higher illness severity during the first 24 h after birth in preterm infants. Ascending intrauterine infection was not associated with high illness severity.     

Family functioning, burden and parenting stress 2 years after very preterm birth

Background

Examining rates of difficulties in family functioning following very preterm birth has been a relatively neglected area of research.

Aims

To examine family functioning, burden and parenting stress in families with very preterm compared with term born children, and investigate influences of parental mental health problems and child neurodevelopmental disability on family outcomes in families with preterm children.

Study design

Participants were 184 very preterm and 71 term children and their parents. Parents completed the Family Assessment Device, Parenting Stress Index and Impact on Family questionnaires when their children were 2 years old (corrected for prematurity). Parental mental health and social risk information were also collected. Children were assessed for neurodevelopmental disability.

Results

Families with very preterm children reported poorer family functioning (p = .03) compared with families with term born children, with less evidence for differences between families with very preterm and term born children in parenting stress and family burden. Within very preterm families, parental mental health problems were associated with higher levels of parenting stress (p = .001), and parents of children with a neurodevelopmental disability were more likely to report higher family burden (p = .04).

Conclusions

For families with very preterm children, parental mental health symptoms and child neurodevelopmental disability may identify families at risk of greater stress and burden who may benefit from additional support.     

Cerebral measurements made using cranial ultrasound in term Ugandan newborns

Background

Few cUS studies of cerebral measurements are available for normal term infants. Normative data is important for evaluating cerebral structure size in symptomatic term infants and assessing preterm brain growth by term age.

Objectives

To (i) make linear measurements using cranial ultrasound (cUS) for major cerebral structures and intracranial spaces in normal newborn term infants, (ii) correlate these measurements with gestational age (GA), birth weight (BW), head circumference (HC), gender and within one infant (iii) examine inter/intra-observer variation, and (iv) compare these data with those currently available.

Design, setting and patients

Linear cUS measurements of major cerebral structures were made in well term-born Ugandan infants at Mulago University Hospital, Kampala. Correlations between the measurements and gender, HC, BW and GA were calculated. Intra- and inter-observer agreements were assessed.

Results

Data from 106 infants (mean GA 39.20 ± 1.4SD weeks) were analysed. Intra/inter-observer agreement was substantial/excellent. Significant correlations were found between HC and pons anterior-posterior diameter (p < 0.01), corpus callosal (CC) length (p = 0.02) and transverse cerebellar diameter (TCD, p < 0.01) and between BW and CC length (p = 0.02), vermis height (< 0.01) and thalamo-occipital distance (p = 0.03); no significant correlation was found with GA. Within infants CC length and TCD correlated significantly (p = 0.019). Males had larger left ventricular indices than females (p = 0.04). The data was similar to those from other populations.

Conclusions

These data provide reliable reference values for linear measurements of many cerebral structures made using cUS. The data agree well with those from other populations suggesting that cerebral size is similar in different ethnic groups.     

Gender-related effects of prenatal administration of estrogen and progesterone receptor antagonists on VEGF and surfactant-proteins and on alveolarisation in the developing piglet lung

Background

Vascular endothelial growth factor (VEGF) is essential for embryonic lung development and has been shown to be regulated by estradiol (E2) and progesterone (P).

Aim

To investigate the effects of prenatal E2 and P withdrawal by specific receptor antagonists on the mRNA expression of VEGF, surfactant proteins (SP-B and SP-C) and on alveolarisation in lung tissue of male and female pig fetuses.

Methods

Fetuses from 10 sows were randomized to receive either both an intramuscular injection of the E2 receptor blocker ICI 182.780 and the P receptor blocker RTI 3021-022 (ICI + RTI, n = 5) or a placebo injection (n = 5) at 90 days of gestation (DOG, 115 = term). After delivery by cesarean section on 114 DOG, tissue of the left lingula of the piglet's lung (28 placebo, 26 ICI + RTI) was obtained to determine the mRNA expression of VEGF, SP-B and SP-C. Lungs from 15 placebo and 14 ICI + RTI group piglets were removed and alveolar counts performed.

Results

The ICI + RTI group showed significantly lower SP-C mRNA expression and alveolar counts compared to the placebo group (p = 0.04 and 0.03, respectively). Diminished alveolarisation in the ICI + RTI group was mainly due to the reduction of alveolar counts in male piglets (p = 0.02). Within the placebo group VEGF and SP-B mRNA expression in male piglets were significantly lower compared to female piglets (p = 0.01 and 0.004, respectively). ICI + RTI treatment abolished this gender-related difference.

Conclusion

Estradiol and P antagonism affected gender-related differences of key proteins for pulmonary function and development and especially in males was associated with diminished alveolarisation.     

Does perinatal asphyxia contribute to neurological dysfunction in preterm infants?

Background

Children born preterm are known to be at risk for neurodevelopmental disorders. The role of perinatal asphyxia in this increased risk is still a matter of debate.

Aim

To analyze the contribution of perinatal asphyxia in a population of preterm infants admitted to a secondary paediatric setting to neurological dysfunction in the first months after birth and to the development of cerebral palsy.

Methods

17 preterm infants with perinatal asphyxia born before 35 weeks postmenstrual age (PMA) and 34 carefully matched preterm controls without asphyxia were studied. Neuromotor outcome was examined by means of three assessments of the quality of general movements (GM) at “preterm” (around 34 weeks PMA), “writhing” (around term age) and “fidgety” GM age (around 3 months post term). Follow-up until at least 18 months corrected age focused on the presence of cerebral palsy (CP).

Results

GM-quality of infants with asphyxia and of those without did not differ. Multivariate analysis revealed that abnormal GMs at “preterm” age were associated with respiratory problems, those at “writhing” age with none of the assessed risk factors, and those at “fidgety” age with the severity of periventricular leukomalacia (PVL) on neonatal ultrasound scan.Perinatal asphyxia was not associated with the development of CP. CP was associated with PVL and the presence of abnormal GMs at “fidgety” age.

Conclusion

Perinatal asphyxia in preterm infants is not associated with an increased risk for neurodevelopmental problems including CP. Respiratory problems during the neonatal period are associated with PVL and adverse neurological outcome.     

Early identification of the risk for free radical-related diseases in preterm newborns

Background

Despite recent advances in preterm newborns healthcare, perinatal pathologies and disabilities are increasing. Oxidative stress (OS) is determinant for the onset of an unbalance between free radicals (FRs) production and antioxidant systems which plays a key role in pathogenesis of pathologies such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), grouped as ‘free radical-related diseases’ (FRD).

Aim

This study tests the hypothesis that OS markers levels in cord blood may predict the onset of FRD pathologies.

Patients and methods

168 preterm newborns of GA: 24-32 weeks (28.09 ± 1.99); and BW: 470-2480 gr (1358.11 ± 454.09) were consecutively recruited. Markers of potential OS risk (non-protein bound iron, NPBI; basal superoxide anion, BSA; under stimulation superoxide anion, USSA) and markers of OS-related damage (total hydroperoxides, TH; advanced oxidation protein products, AOPP) were assessed in cord blood. Associations between FRD onset and OS markers were checked through inferential analysis (univariate logistic regression).

Results

The development of FRD was significantly associated to high cord blood levels of TH, AOPP and NPBI (respectively p = 0.000, OR = 1.025, 95%CI = 1.013-1.038; p = 0.014, OR = 1.092, 95%CI = 1.018-1.172; p = 0.007, OR = 1.26995%CI = 1.066-1.511).

Conclusions

Elevated levels of TH, AOPP and, above all, NPBI, in cord blood are associated with increased risk for FRD. OS markers allow the early identification of infants at risk for FRD because of perinatal oxidant exposure. This can be useful in devising strategies to prevent or ameliorate perinatal outcome.     

Uniform treatment thresholds for hyperbilirubinemia in preterm infants: background and synopsis of a national guideline

Background

To prevent severe hyperbilirubinemia and bilirubin neurotoxicity, the American Academy of Pediatrics' management guideline for hyperbilirubinemia in near term infants is used worldwide. A leading guideline for jaundiced preterm infants is lacking whereas the risk on severe hyperbilirubinemia is high in these infants. Our aim was to define uniform treatment thresholds for jaundiced preterm infants. In this article we present the history and a synopsis of this novel national guideline.

Study Design

A survey on guidelines for hyperbilirubinemia in preterm infants was sent to all Dutch Neonatal Intensive Care Units (NICUs). After comparison with international guidelines, a new consensus-based guideline was developed.

Results

Treatment thresholds of all 10 NICUs were based on Total Serum Bilirubin (TSB) and related to birth weight (n = 9) and gestational age (n = 1). NICUs used age-specific (n = 6) or fixed (n = 4) TSB-thresholds resulting in a large range of thresholds (maximal 170 μmol/L for phototherapy and 125 μmol/L for exchange transfusion). Acidosis, asphyxia, sepsis, active hemolysis and intraventricular hemorrhage were the most frequently used risk factors. Consensus was agreed upon TSB-based treatment thresholds, categorized in 5 birth weight groups and divided in high and low risk infants.

Conclusion

There was no standardized care for jaundiced preterm infants in the Netherlands. In addition to the internationally used guideline for (near) term infants, a novel “consensus based” guideline for preterm infants with a gestational age of less than 35 weeks has been developed and implemented in the Netherlands. This guideline is approved and recommended by the Dutch Society of Pediatrics.     

Postnatal growth of preterm born children ≤ 750g at birth

Background

Extremely low birth weight (ELBW) infants are at risk of impaired postnatal growth. Impaired postnatal growth has been reported to be associated with delayed cognitive and motor development.

Aims

To describe postnatal growth patterns of appropriate and small for gestational age (AGA and SGA) ELBW children in relation to their cognitive and motor outcome at age 5.5.

Study design

Retrospective cohort study.

Subjects

One hundred one children with a BW ≤ 750 g, born between 1996 and 2005 in the University Hospital Utrecht, The Netherlands.

Outcome measures

Height (Ht), weight (Wt), occipital-frontal circumference (OFC) at birth, 15 months and 2 years corrected age and 3.5 and 5.5 years.Cognitive and motor outcome at 5.5 years of age, classified as normal (Z-score ≥−1), mildly delayed (−2 ≤ Z-score <−1) or severely delayed (Z-score <−2). AGA (Ht, Wt or OFC at birth ≥−2 SDS) infants were compared with SGA (Ht, Wt or OFC at birth <−2 SDS) infants.

Results

Between birth and 5.5 years catch-up growth in Ht, weight for height (Wt/Ht), Wt and OFC was seen in 72.2%, 55.2%, 28.6% and 68.9% respectively of the SGA infants. For AGA infants we found substantial catch-down growth in Ht (15.4%) and Wt (33.8%). Cognitive and motor outcome was normal in 76.2% and 41.6% of the 101 children. A significantly higher percentage of normal cognitive outcome was found in AGA infants with Wt growth remaining at ≥−2 SDS compared to AGA infants with catch-down growth (83% vs 63%). Next, SGA infants who caught-up in OFC had a higher prevalence of normal cognitive outcome compared to SGA infants who did not catch-up in OFC. Furthermore, a higher percentage of severely delayed motor outcome was found in SGA infants without catch-up growth in Wt compared to SGA infants who caught-up in Wt (61.5% vs 32.2%).

Conclusions

Catch-up growth in Ht, Wt/Ht and OFC occurred in the majority of the SGA infants with a BW ≤ 750 g, but was less common in Wt. AGA children who remained their Wt at ≥−2 SDS have a better cognitive and motor developmental outcome at 5.5 years of age. Catch-up growth in OFC was associated with a better cognitive outcome at 5.5 years of age.     

Acute cardiovascular responses in preterm infants at 34–39 weeks of gestational age

Background

Premature infants demonstrate immature physiological control mechanisms; however their acute cardiovascular control has not yet been widely studied.

Aim

The aim of this study was to analyze heart rate (HR) and blood pressure (BP) control in preterm infants.

Subjects

Twenty preterm infants with a mean gestational age of 31 ± 2.4 (26–34) weeks at birth were evaluated at a gestational age of 36 ± 1.5 (34–39) weeks. Results were compared to twenty, healthy, full-term, control infants studied at the age of 12 ± 3 weeks.

Outcome measures

HR and BP responses to 45° head-up tilt and side motion tests during non-rapid eye movement sleep were analyzed. In addition, HR responses to spontaneous arousals from non-rapid eye movement sleep were evaluated.

Results

Preterm infants showed significantly smaller initial HR and BP responses compared with controls in head-up tilt (HR p = 0.0005, systolic BP p = 0.02, diastolic BP p = 0.01) and side motion tests (HR p = 0.002, systolic BP p < 0.0001, diastolic BP p < 0.0001). Furthermore, in tilt tests, preterm infants presented with greater intersubject variability in BP responses than controls (systolic BP p = 0.009, diastolic BP p = 0005). Preterm HR responses to spontaneous arousals were similar to controls.

Conclusions

This study indicates immature vestibulo-mediated cardiovascular control in preterm infants compared with term infants. This is seen as attenuated BP responses to side motion test and more labile acute BP control to postural challenge.