Early Human Development

Editorial Board

2012-01-01

Introductory editorial: Prenatal diagnosis and fetal surgery

Kokila Lakhoo — 2012-01-01

Despite improvements in perinatal care serious birth defects still account for 20% of all deaths in the newborn period and an even greater percentage of serious morbidity later in infancy and childhood. The major causes of congenital malformation are chromosomal abnormalities, mutant genes, multifactorial disorders and teratogenic agents. Prenatal diagnosis has remarkably improved our understanding of congenital structural anomalies, however the diagnosis and management of these complex fetal anomalies, require a multidisciplinary team encompassing obstetricians, neonatologists, geneticists, paediatricians, paediatric surgeons and occasional other specialist with expertise to deal with all the maternal and fetal complexities.

Prenatal diagnosis: Types and techniques

S.L. Collins, L. Impey — 2012-01-01

Abstract: Up to 3% of UK pregnancies will be affected by congenital abnormality. Prenatal diagnosis allows the parents to make informed decisions about their pregnancy, healthcare professionals to optimise the antenatal care and families prepare for the birth of the baby. There are many techniques employed which range from the non-invasive ultrasonography to the highly invasive amniocentesis. This review explores the methods currently available in the UK as well as considering the newer minimally-invasive technologies available including cell-free fetal DNA and pre-implantation genetic diagnosis.

Fetal counselling for surgical conditions

Kokila Lakhoo — 2012-01-01

Abstract: Foetal counselling is best achieved by a multidisciplinary team that can favourably influence the perinatal management of prenatally diagnosed anomalies and provide this information to prospective parents. Prenatal diagnosis has remarkably improved our understanding of surgically correctable congenital malformations. It has allowed us to influence the delivery of the baby, offer prenatal surgical management and discuss the options of termination of pregnancy for seriously handicapping or lethal conditions. Antenatal diagnosis has also defined an in utero mortality for some lesions such as diaphragmatic hernia and sacrococcygeal teratoma so that true outcomes can be measured. The limitation of in-utero diagnosis cannot be ignored. The aim of prenatal counselling is to provide information to prospective parents on foetal outcomes, possible interventions, appropriate setting, time and route of delivery and expected postnatal outcomes, immediate and long term.

Best practice guidelines: Fetal surgery

Nada Sudhakaran, Uma Sothinathan, Shailesh Patel — 2012-01-01

Abstract: Fetal intervention encompasses a range of procedures on the fetus with congenital structural anomalies, whilst still on the placental circulation. The concept of fetal surgery was conceived in order to prevent fetal or early postnatal death, or to prevent permanent irreversible organ damage. The benefit of these procedures has to be balanced with risks to both the mother and the fetus. Open fetal surgery, more commonly conducted in North American centres, involves open surgery to the uterus in order to operate on the fetus. Fetal intervention centres in Europe more commonly use minimally invasive fetoscopic surgery. This paper elaborates on the various strategies used in dealing with anomalies of different organ systems of the fetus.

Skin conductance measurements as pain assessment in newborn infants born at 22–27weeks gestational age at different postnatal age

Josanne Munsters, Linda Wallström, Johan Ågren, Torgny Norsted, Richard Sindelar — 2012-01-01

Abstract: Background: To assess pain or stress in newborn infants submitted to intensive care is important but difficult, as different observational pain scales are not always reliable in premature infants. As an indicator of pain, skin conductance (SC) measurements have detected increased sweating in newborn infants >28 gestational age (GA) submitted to heel lancing.Objective: To measure SC during heel lancing and routine care in newborn infants, born at 22 to 27 GA, with special relation to postnatal age (PNA).Methods: In six infants <28+0 GA and 4 infants ≥28+0 GA spontaneous SC activity and behavioural state (Neonatal Pain Agitation and Sedation Scale (N-PASS)) was measured before, during and after each intervention. Measurements were repeated in each patient at different PNA.Results: Baseline SC prior to intervention took longer time to stabilise and was higher in <28 than in ≥28+0 PNA. The combination of heel lancing and squeezing gave an increased SC in <28 PNA, whereas heel lancing alone gave the same SC response in ≥28+0 PNA. A possibly continued immature response in SC measurements was not observed. Oral glucose admission prior to heel lancing increased SC. Routine care did not give any changes in SC. Except during orogastric tube placement no signs of discomfort or pain could be detected by the neonatal pain, agitation and sedation scale (N-PASS) in <28 PNA.Conclusion: Changes in SC could be detected in infants at <28+0 PNA and related to the combination of heel lancing and squeezing. A maturational development of the SC was observed in infants born <28 GA. SC seems to be able to differentiate between pain and discomfort.

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

B. Resch, K. Neubauer, N. Hofer, E. Resch, U. Maurer, J. Haas, W. Müller — 2012-01-01

Abstract: 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 35weeks 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 10min 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. 15h, p=.033). Neurodevelopmental follow-up at a median time of 46months 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.Highlights: ► Besides preterm premature rupture of the membranes and chorioamnionitis early-onset sepsis remains an additional risk factor fort he development of cystic PVL. ► The association between hypocarbia and PVL is stringent. However, the individual risk assessment is difficult in clinical routine. ► Neurodevelopmental follow-up of infants with cystic PVL reveals adverse neurological outcome in the majority of infants.

Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period

2012-01-01

Abstract: Background: Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs).Objective: To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome.Design/methods: We included 82 children (born 1998–2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP).Results: Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e., death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98–7.69; P=.055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42–32.82, P=.016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90–5.36; P<.001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99–32.97, P=.051. We found no association between seizure aetiology and outcome.Conclusions: In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.

Is it possible to predict the infant's neurodevelopmental outcome at 14months of age by means of a single preterm assessment of General Movements?

2012-01-01

Abstract: Background: It continues to be a challenge for clinicians to identify preterm infants likely to experience subsequent neurodevelopmental deficits. The Test of Infant Motor Performance (TIMP) and the assessment of spontaneous general movements (GMs) are the only reliable diagnostic and predictive tools for the functionality of the developing nervous system, if applied before term.Aim: To determine to what extent singular preterm assessments of motor performance can predict the neurodevelopmental outcome in 14-month olds.Methods: Thirty-seven preterm infants born <34weeks gestational age were recruited for the study at the NICU of the São Lucas University Hospital, Porto Alegre, RS, Brazil. At 34weeks, their GMs were assessed; and the Test of Infant Motor Performance (TIMP) was applied. A prospective design was used to examine (A) the association between the GM assessment and the TIMP; and (B) the relation between GMs or the TIMP and the developmental status at 14months, assessed by means of Alberta Infant Motor Scales (AIMS) and the Pediatric Evaluation of Disability Inventory (PEDI).Results: Nineteen infants (41%) had abnormal GMs; only one scored within the TIMP average range. Hence, GMs and TIMP were not related. Children with cramped-synchronized GMs at 34weeks preterm had a lower AIMS centile rank than those with poor repertoire or normal GMs. There was a marginal association between cramped-synchronized GMs and a lower PEDI mobility score.Conclusions: A single preterm GM assessment is only fairly to moderately associated with the 14-month motor development. The TIMP is not suitable as a complementary assessment tool at such a young age.

Parenting stress in mothers of preterm infants during early infancy

Peter H. Gray, Dawn M. Edwards, Michael J. O'Callaghan, Monica Cuskelly — 2012-01-01

Abstract: Objective: Mothers of preterm infants during the first year of life may experience stresses greater that those found in mothers of term infants. The aim of the study was to determine the levels of parenting stress and psychological well-being in mothers of very preterm babies in comparison to a control group of term mothers.Methods: One hundred and five mothers who delivered 124 babies at ≤30weeks gestation were recruited together with 105 mothers who delivered 120 babies at term. At 4months of age (corrected for prematurity for the preterm babies), the mothers completed the Parenting Stress Index Short Form, the Edinburgh Postnatal Depression Scale (EPDS), the Dyadic Adjustment Scale (DAS) and the Short Temperament Scale for Infants (STSI). The preterm and term groups were compared.Results: Questionnaires were returned from 86 of the preterm mothers and 97 of the term mothers. The mean Total Stress score for the preterm and term groups was 67.0 and 63.79 respectively (P=0.32) with 17% of the preterm and 9% of the term group having high scores (P=0.135). There were no differences of the EPDS and the DAS between the groups. The temperament of the preterm infants was similar to the term infants. For both groups, scores on the EPDS, DAS and the STSI were independent predictors of Total Stress scores on multiple regression analysis.Conclusion: Parenting stress in mothers of preterm infants during early infancy does not appear to be greater than that in mothers of infants born at term. For both groups of mothers, depression symptoms, marital satisfaction and infant temperament were independent risk factors for high levels of parenting stress.

Validation of transcutaneous bilirubin nomogram in identifying neonates not at risk of hyperbilirubinaemia: A prospective, observational, multicenter study

2012-01-01

Abstract: Background: Transcutaneous bilirubin (TcB) measurement is widely used as screening for neonatal hyperbilirubinaemia.Aims: To prospectively validate TcB measurement using hour-specific nomogram in identifying newborn infants not at risk for severe hyperbilirubinaemia.Study design: prospective, observational, multicenter.Subjects: 2167 term and late preterm infants born in 5 neonatal units in the Lazio region of Italy.Methods: All neonates had simultaneous TcB and total serum bilirubin (TSB) measurements, when jaundice appeared and/or before hospital discharge. TcB and TSB values were plotted on a percentile-based hour-specific transcutaneous nomogram previously developed, to identify the safe percentile able to predict subsequent significant hyperbilirubinaemia defined as serum bilirubin >17mg/dL or need for phototherapy.Results: Fifty-five babies (2.5%) developed significant hyperbilirubinaemia. The 50th percentile of our nomogram was able to identify all babies who were at risk of significant hyperbilirubinaemia, but with a high false positive rate. Using the 75th percentile, two false negatives reduced sensitivity in the first 48 hours but we were able to detect all babies at risk after the 48th hour of age. Conclusions: This study demonstrates that the 75th percentile of our TcB nomogram is able to exclude any subsequent severe hyperbilirubinaemia from 48h of life ahead.

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

Danuta Chrzanowska-Liszewska, Joanna Seliga-Siwecka, Maria K. Kornacka — 2012-01-01

Abstract: 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 0–3days 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.

Higher incidence of thyroid agenesis in Mexican newborns with congenital hypothyroidism associated with birth defects

2012-01-01

Abstract: Background: Congenital hypothyroidism (CH) is the most common endocrine system disorder in newborns. Ectopic thyroid and agenesis are the most frequent thyroid structural malformations. Several reports have shown that CH is associated with birth defects (BD) ranging from congenital heart disease to ocular and gastrointestinal anomalies.Aims: We investigated how many and what types of BD were associated with CH in Mexican children.Study design: Cross-sectional study conducted in patients with confirmed CH.Setting: Highly specialized government pediatric center in Mexico City.Subjects: We included 212 patients with permanent CH identified by newborn screening.Results: We found that 24% of patients with CH also had BD, and that there was a higher prevalence of thyroid agenesis in the group of patients with CH associated with BD (CH+BD) versus the isolated CH group (p=0.007). There were more females than males in both groups. The most common BD were congenital heart diseases, especially those of the atrial septum, followed by patent ductus arteriosus, found as a single malformation or as part of a complex congenital heart disease. In this study, we found Hirschsprung disease, Beckwith–Wiedemann syndrome, Pierre Robin sequence, Albright's osteodystrophy, VATER association, and frontonasal dysplasia associated with CH.Conclusions: In this study population, there was a high prevalence of BD in patients with permanent CH. Thyroid agenesis was the main etiological cause of CH in patients with associated congenital malformations. The high prevalence of CH+BD underlines the need for a comprehensive clinical diagnostic approach of the patients with CH.