Neurodevelopmental outcome after COX inhibitor treatment for patent ductus arteriosus

Aim

To compare neurodevelopmental results in very low birth weight (VLBW) infants two years after successful or failed cyclooxygenase inhibitor treatment with either indomethacin or ibuprofen for a haemodynamically significant patent ductus arteriosus (hsPDA).

Methods

We retrospectively evaluated closure rates and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with indomethacin and 93 with ibuprofen.

Results

Indomethacin and ibuprofen therapy groups did not differ in their baseline clinical profile (median gestational age 26.0 and 26.2 wks d) in early (median CRIB 6 and 5, respiratory distress > 2° in 36 and 34 infants) and late morbidities (intraventricular hemorrhage > 2° in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80 and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome. The therapy failure group (54 infants) was characterized by lower median gestational age (25.0 wks d) and higher mortality (17%). No differences were found in the neurodevelopmental outcome of the surviving infants with ligation as compared to the survivors with successful pharmacological closure of the PDA at 24 months corrected age.

Conclusion

Use of either ibuprofen or indomethacin for closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW infants.     

Endothelial progenitor cells, bronchopulmonary dysplasia and other short-term outcomes of extremely preterm birth

Aim

To evaluate the impact of endothelial progenitor cells (EPCs), a subset of committed circulatory stem cells, on the development of bronchopulmonary dysplasia (BPD) and other short term outcomes in a cohort of extremely premature newborns.

Methods

Progenitor cells were quantified by flow cytometry at birth in 36 neonates born <=28 weeks of gestation and at 36 postmenstrual weeks in 18 of them. Cells expressing the stemness markers CD34, CD133, or both were defined as circulating progenitor cells (CPCs). EPCs were defined as CPCs co-expressing the endothelial marker KDR.

Results

Mean (SD) gestational age and birth weight of the infants studied were 26.2(1.5) weeks and 761.6(171.8) grams, respectively. EPC levels at birth did not differ between infants who subsequently developed BPD (n = 9) and those who did not (n = 24) [CD34⁺KDR⁺ EPCs: 81(34-41) vs 80(56-110), p = 0.7] and were not correlated with the duration of mechanical ventilation or O2-dependence, nor with the need of surfactant replacement. Infants with a hemodynamically significant patent ductus arteriosus (PDA) (n = 22) had significantly lower EPC levels at birth than those with no PDA (n = 11) [CD34⁺KDR⁺ cells: 47(34-92) vs 142(84.5-221), p = 0.008]. Data from the 18 infants studied both at birth and at 36 postmenstrual weeks showed that, while CPCs sharply decline over time, levels of all EPCs phenotypes are preserved after delivery.

Conclusions

Levels of EPCs at birth did not affect the risk of developing BPD in our group of extremely premature neonates. However, the association between low EPC counts at birth and PDA may be clinically relevant, and deserves further studies.     

Echocardiography predicts closure of patent ductus arteriosus in response to ibuprofen in infants less than 28 week gestational age

Background

Patent ductus arteriosus (PDA) is a frequent problem in preterm infants, and its incidence is inversely correlated with gestational age. The efficacy of medical treatment decreases with decreasing gestational age (GA), and failure rates as well as ductus ligation rates of 40% have been reported in < 28 week GA newborns. The aim of this study was to determine whether echocardiographic parameters can predict response to ibuprofen treatment of PDA.

Study design

In a longitudinal study, 29 infants born < 28 week GA were screened for a significant PDA (left atrial to aortic root ratio > 1.4, anterior cerebral artery resistance index > 0.8, and oxygen requirement > 35%) at 24-72 h of life and, if a PDA was found, treated with 10-5-5 mg/kg ibuprofen intravenously every 24 h. Ductal parameters were monitored by serial echocardiography. Infant neurodevelopmental outcomes were assessed at 24 month corrected age.

Results

All 15 infants with significant PDA responded to the ibuprofen loading dose indicated by reduced PDA diameters or increased PDA maximum flow velocities (PDA V_max), and 7 patients showed an ongoing response resulting in a closed PDA after the 1st cycle (47%). Of the 8 non-responders, 7 received a 2nd cycle with 2 further responders (29%). All non-responders to the 2nd course had a PDA V_max ≤ 180 cm/s and increasing ductal diameters after the 3rd ibuprofen dose of the 1st course.

Conclusion

Maximum flow velocity and diameter of the PDA at the end of the 1st cycle discriminate between responders and non-responders to further ibuprofen treatment.     

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

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.     

High-Dose Oral Ibuprofen in Treatment of Patent Ductus Arteriosus in Full-Term Neonates

Background:

Patent ductus arteriosus (PDA) is an important risk for heart failure due to left to right shunt in term neonates.

Objectives:

In this study, we evaluated the effect of high dose ibuprofen in closure of PDA in term neonates.

Patients and Methods:

We used double dose ibuprofen (20 mg/kg, 10 mg/kg, and 10 mg/kg) for 3 - 30 day old term neonates with PDA who were admitted in the neonatal wards of Shiraz University of Medical Sciences. The results of this study were compared to the data of the previous study in our center which used the low dose of ibuprofen (10 mg/kg, 5 mg/kg, and 5 mg/kg).

Results:

29 full term neonates received high-dose ibuprofen, in 18 neonates, PDA was closed after 4 days (62.1% versus 43.3% for the standard dose and 4.7% for the control group in the previous study) (P = 0.001). The results showed no significant correlation between the closure rate and gestational age, postnatal age, sex, and weight. In the 4^th day of treatment, size of the pulmonic end of ductus arteriosus decreased from 2.09 mm to 0.77 mm compared to 1.68 mm to 0.81 mm in the standard dose of oral ibuprofen and 2.1 mm to 1.4 mm in the control group (P = 0.046).

Conclusions:

This study indicated that high-dose oral ibuprofen was more effective in closing or decreasing the size of PDA.     

Insufficient intimal thickening and scarcity of cell deaths may play a significant role in the pathogenesis of the persistently patent ductus arteriosus in the preterm infant

Background

Functional closure and subsequent remodeling of the ductus arteriosus (DA) are essential for postnatal adaptation. Very preterm infants often fail to accomplish this process spontaneously. Histologic studies on human DA have shown that the closing ductus exhibits progressive intimal thickening and cell death of muscle media, which was verified by recent animal studies.

Aims

To analyze the histologic findings of preterm infants' DA in relation to their clinical parameters and to investigate the histologic difference between preterm and term DAs.

Methods

Histology of 14 preterm DAs and 13 term DAs obtained from surgery was analyzed. We examined hematoxylin and eosin staining and van Gieson staining for the elastic tissue. Cell death was determined with the in situ apoptosis detection technique.

Results

The histologic findings of preterm DAs showed apparent correlations with clinical parameters, especially birth weight. Preterm DA histology was significantly different from that of term DAs in the extent and degree of intimal thickening. Cytolytic necrosis where TUNEL-positive cell deaths were prominent was observed mainly in term DAs.

Conclusions

The results of this study indicate that insufficient intimal thickening and scarcity of cell deaths in the DA may play a significant role in the pathogenesis of the persistently patent DA in preterm infants.     

Utilidad del propéptido natriurético cerebral en el diagnóstico y manejo del ductus arterioso permeable

Introduction

Patent ductus arteriosus (PDA) is a prevalent condition in preterm infants, and may be related to increased morbidity and mortality in the most immature newborns. Recent studies have examined the usefulness of brain natriuretic propeptide (proBNP) in the diagnosis of this pathology. The aim of the study was to evaluate the diagnostic efficacy of proBNP as a marker of hemodynamic overload in PDA.

Does primary surgical closure of the patent ductus arteriosus in infants <1500 g or ≤32 weeks’ gestation reduce the incidence of necrotizing enterocolitis?

BACKGROUND:

The hemodynamic perturbation related to patent ductus arteriosus (PDA) is associated with a higher risk of necrotizing enterocolitis (NEC).

OBJECTIVE:

To determine whether primary surgical closure, as compared with treatment with indomethacin or exposure to prophylactic indomethacin, reduces the incidence of NEC in preterm infants <1500 g and/or ≤32 weeks’ gestation with clinically and echocardiogram-identified PDA.

METHODS:

The literature was reviewed using the methodology for systematic reviews for the Consensus of Science adapted from the American Heart Association’s International Liaison Committee on Resuscitation.

RESULTS:

Ten studies were reviewed. The incidence of NEC was not lower in infants who underwent primary surgery for closure of the PDA compared with infants treated with indomethacin or infants exposed to prophylactic indomethacin (level of evidence 2).

CONCLUSION:

Primary surgical closure of the PDA cannot be recommended as an intervention to decrease the incidence of NEC in infants <1500 g and/or ≤32 weeks’ gestation.     

Cardiovascular biomarkers pro-atrial natriuretic peptide and pro-endothelin-1 to monitor ductus arteriosus evolution in very preterm infants

Background

The diagnostic and prognostic appraisal of patent ductus arteriosus (PDA) in preterm infants is still debatable.

Aims

To compare plasma cardiovascular biomarkers with echocardiographic indices alongside ductus arteriosus (DA) evolution in very preterm infants within the first week of life.

Methods

Mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET-1) levels were prospectively measured on the second and sixth days of life (DOL) in 52 preterm infants born before 32 weeks of gestation. Echocardiographic indices to define DA patency and significance were simultaneously obtained. Logistic regression and receiver operating characteristics (ROC) analyses were used to assess and quantify the biomarkers' diagnostic capacities.

Results

Thirty infants exhibited PDA on DOL 2; in 21 of these infants, DA was characterized as hemodynamically significant. Treatment failure after a first course of indomethacin was noted in 8 infants (DOL 6), whereas 7 participants underwent later surgical ligation. The diagnostic accuracy of cardiovascular biomarkers was moderate on DOL 2 but high on DOL 6. PDA was the only significant predictor of MR-proANP levels on DOL 6, independent of the effect of clinical confounders (regression coefficient 0.426, R² 0.60). Infants with MR-proANP ≥ 850 pmol/l on DOL 2 had 3.9-fold higher risk (95% CI 1.01 to 14.5) of being diagnosed with significant DA, whereas infants with MR-proANP ≥ 700 pmol/l on DOL 6 had 7.1-fold higher risk (1.9 to 27.2) for pharmaceutical treatment failure.

Conclusion

The cardiovascular plasma biomarker MR-proANP is a promising candidate for monitoring PDA evolution in very preterm infants.     

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

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 > 17 mg/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 48 h of life ahead.     

Effect of ibuprofen on bilirubin-albumin binding in vitro at concentrations observed during treatment of patent ductus arteriosus

Background

In vitro studies have shown that ibuprofen (IBU) may interfere with bilirubin-albumin binding at concentrations of 100 µg/mL and above.

Objectives

The present study evaluates the in vitro bilirubin displacement over the range of IBU plasma concentrations observed in vivo during curative treatment of patent ductus arteriosus in preterm infants.

Methods

Considering that individual plasma concentrations obtained during the clinical development of IBU in preterm infants were ranging between 10 and 70 µg/mL and exceptionally above 100 µg/mL, we used the modified peroxidase method to determine total and unbound bilirubin concentrations without IBU and with IBU over this specific concentration range.

Results

Total bilirubin and albumin concentrations were respectively 6.6 mg/dL and 2.87 g/dL in pooled newborn plasma. No displacement of bilirubin from its albumin binding sites by IBU was observed over a range of concentrations from 10 to 100 µg/mL. Only a concentration of 200 µg/mL significantly increased the unbound bilirubin by 1.5-fold (p = 0.0008).

Conclusions

This in vitro study confirms displacement of bilirubin by a high IBU concentration of 200 µg/mL, however it retrieves no significant displacement over a range of concentrations up to and including 100 µg/mL, i.e. within the range of in vivo concentrations at the recommended dose regimen.     

Low platelet count is associated with ductus arteriosus patency in preterm newborns

Background/aim

To determine whether there is an association between platelet counts and patent ductus arteriosus (PDA) incidence and/or closure in preterm newborns.

Study design and subjects

Premature infants with hemodynamically significant PDA (n = 154) and a control group without PDA (n = 207) who were hospitalized in the NICU were retrospectively evaluated. Platelet counts and other platelet indices including mean platelet volume (MPV) and platelet distribution width (PDW) of the infants in both groups during the first 3 days of life were recorded. Ibuprofen was started in infants with hemodynamically significant PDA and echocardiography was repeated 48 h thereafter to assess the closure of ductus.

Results

Median gestational age and birth weight of the infants with PDA were 28 (range 26–29) weeks and 1060 (range 892–1250) g respectively. Platelet counts were significantly lower in the patient group than in the control group (p < 0.001). Multivariate analysis including gestational age, presence of RDS, presence of thrombocytopenia and PDW showed that hemodynamically significant PDA was independently associated with platelet count < 150,000 (OR = 2.13, 95% CI 1.26–3.61; p = 0.005), high PDW (> 17) (OR = 2.68, 95% CI 1.41–5.09; p = 0.003) and the presence of RDS (OR = 2.25, 95% CI 1.41–3.59; p = 0.001). Baseline platelet counts of the infants in whom ductus closed or persisted after ibuprofen treatment were similar.

Conclusions

PDA was associated with low platelet count and high PDW but not with other platelet indices in preterm infants. We could not show an association between platelet counts and persistence or closure after medical treatment.     

Patent ductus arteriosus in preterm infants is associated with cardiac autonomic alteration and predominant parasympathetic stimulation

Background

Hemodynamic disorders in patent ductus arteriosus (PDA) may alter the stimulation of the autonomic nervous system.

Aim

The objective of this study was to analyze the orthosympathetic–parasympathetic balance in preterm infants with PDA.

Study design and subjects

Patients were included from consecutive admissions to Amiens University Hospital from 2009 to 2011. We defined a PDA group and a Control group (echographic criteria). For each patient, three 4-minutes segments of ECG were recorded during quiet sleep and the RR chronologic series were extracted, and spectral (Fourier Transform) and time-domain analyses were performed. For each parameter of heart rate variability (HRV), average of three measures was determined and analysed.

Results

Forty-four patients were included for analysis. The total HRV power, LF/HF ratio and SDNN were lower in the PDA group (n = 22, gestational age 28.2 w ± 1.9) than in the Control group (n = 22, gestational age 28.8 w ± 2). The decrease in LF power destabilized the autonomic balance in favour of parasympathetic stimulation. After adjustment for postconceptional age, PDA was still associated with parameters of autonomic neural stimulation.

Conclusion

These results suggest association of PDA with predominance of parasympathetic stimulation in preterm infants. The mechanisms of homeostasis in patients with PDA are very complex and involve both circulatory adaptations and control by autonomic pathway. If confirmed, our results could be interesting for future researches aiming to verify the interest of new targeted therapies for the management of PDA.     

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.     

Impact of patient selection on outcomes of PDA in very low birth weight infants

Aim

The aim of this study was to observe whether our patient selection maximized the benefits of PDA ligation by comparing the outcomes in a surgically ligated group of PDA to a medically closed group.

Study design

If a hemodynamically significant ductus arteriosus (HSDA) was found to meet both clinical and echocardiographic criteria (stage ≥ 3), as proposed by NcNamara and Hellman, medical treatment was initiated with oral ibuprofen (maximum 2 courses). If the PDA of these patients failed to close medically, timed surgical closure was performed.

Result

Medical treatment was effective in 75 (72%) cases, and 29 (28%) patients required surgical ligation. The mean gestational age and birth weight were each significantly lower and the initial PDA shunt size was significantly larger in the surgically treated group. Additionally, the mean durations of mechanical ventilation, oxygen dependence and hospital admission were significantly longer in the surgically ligated group. However, our logistic regression analysis demonstrated no statistically significant difference in the outcomes of hospitalization (CLD, NEC, ARF, sepsis, IVH, ROP, PVL and death) between the two groups.

Conclusion

Comprehensive HSDA patient selection may maximize the benefits of timed PDA ligation without adverse outcomes in very low birth weight infants.     

Cierre quirúrgico del ductus arterioso persistente del prematuro: ¿influye la técnica quirúrgica en los resultados?

Introduction

Surgical closure of patent ductus arteriosus in premature neonates is an aggressive technique and is not free of complications. A study was designed with the aim of describing our experience with a less invasive technique, the extra-pleural approach via a posterior minithoracotomy, and to compare the results with the classic transpleural approach.

The quality of fetal arm movements as indicators of fetal stress

Background

Although a number of studies have found that maternal stress affects the fetus, it is unclear whether jerky fetal movements observed on ultrasound scans are indicative of fetal stress, or whether they are part of normal development.

Aims

The present study was designed to examine the relationship between jerky fetal arm movements in relation to fetal age and stress.

Methods

Video recordings were made of routine ultrasound scans of 57 fetuses (age range 8 to 33 weeks) classified into three age groups: 1st trimester (8-12 weeks, N = 9), 2nd trimester (13-24 weeks, N = 38), and 3rd trimester (26-33 weeks, N = 10). Following previous research on stress behaviour in neonates, a fetal index of stress was derived from frequency of hiccup, back arch and rhythmical mouthing.

Results

Results indicated that while stress level was unrelated to fetal age, jerkiness of arm movements was significantly associated with the fetal stress index but not age.

Conclusions

Our findings suggest that jerky arm movements in fetuses are suggestive of fetal stress.     

Pain reactivity and recovery in preterm neonates: latency, magnitude, and duration of behavioral responses

Background

Studies on acute-procedural pain in neonates have been based more on single behavioral scores than on response patterns.

Aim

To assess the individual reactivity and recovery pattern to the painful procedure of blood collection.

Study design

A cross-sectional, within-group comparison trial.

Subjects

Forty-eight preterm and very low birth weight neonates hospitalized in a Neonatal Intensive Care Unit.

Outcome measures

The assessment was divided into five consecutive phases: Baseline (BL); Antisepsis (A), covering the period of handling of the neonate for antisepsis prior to puncture; Puncture (P); Recovery-Dressing (RD), covering the period of handling of the neonate for dressing until positioning for rest in the isolette; and Recovery-Resting (RR). Facial activity was recorded by video, and sleep-wake state was recorded at the bedside. The facial activity of the neonates was analyzed according to Neonatal Facial Coding System (NFCS). The pain reactivity pattern was analyzed using the measures of latency, magnitude, and duration of behavioral responses and by comparison between the different phases.

Results

In the Antisepsis phase, the neonates showed higher NFCS score and behavioral arousal than at Baseline. In the Puncture phase, the neonates showed higher NFCS score and behavioral activation than in Baseline and in Antisepsis. In Recovery-Dressing, 31% of neonates continued to show more behavioral activation than at Baseline.

Conclusion

To better assess and manage pain in preterm neonates, it is relevant to analyze the individual patterns of changes, focusing on the reactivity and also the recovery, during painful stimuli.     

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.     

Determinants of morbidity in late preterm infants

Objective

To assess the effect of selected maternal medical conditions and complications of pregnancy on the risk for morbidity among late preterm neonates.

Design

Prospective cohort study.

Material and methods

A total of 548 late preterm neonates (34^0/7 to 36^6/7 weeks' gestation) delivered from August 2006 to July 2009, were included. Information regarding demographics, gestational age, mode of delivery, maternal age and parity, pre-existing medical conditions and complications of pregnancy were obtained and associated with neonatal morbidity, both independently and as joint exposures. Newborn morbidity was defined by combining specific diagnoses, length of hospital stay, and transfer to the Neonatal Intensive Care Unit.

Results

Overall, 165 (30.1%) of the late preterm infants suffered from morbidity. The morbidity rates were 16.8% at 36 weeks' gestation, and then approximately doubled from 38.2% at 35 weeks to 59.7% at 34 weeks. The joint effect of gestational age (OR 8.43 for 34 weeks and 3.60 for 35 weeks' gestation), small for gestational age (SGA) (OR 4.18), multiple gestation (OR 3.68) and lack of antenatal steroid administration (OR 4.03), was greater than the independent effect of each of these factors, and greater than additive. Emergency caesarean section (OR 1.43) and antepartum haemorrhage (OR 3.07) were also associated with a significant impact on neonatal morbidity.

Conclusions

The risk for morbidity among late preterm infants, changes with each passing week of gestation. This risk seems to be intensified, when other exposures such as SGA, multiple gestation, emergency caesarean section, lack of antenatal steroid administration and antepartum haemorrhage, are also present.