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Concept: Preterm birth

277

Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice.

Concepts: Childbirth, Infant, Epidemiology, Medical statistics, Infant mortality, Preterm birth, Perinatal mortality, Human Development Index

167

The term “encephalopathy of prematurity” encompasses not only the acute brain injury [such as intraventricular hemorrhage (IVH)] but also complex disturbance on the infant’s subsequent brain development. In premature infants, the most frequent recognized source of brain injury is IVH and periventricular leukomalacia (PVL). Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury, and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD), and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP, and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9, and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after PHVD. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

Concepts: Childbirth, Infant, Infant mortality, Pediatrics, Cerebrospinal fluid, Periventricular leukomalacia, Preterm birth

166

Preterm infants are at increased risk of language-related problems later in life; however, few studies have examined the effects of preterm birth on cerebral responses to speech at very early developmental stages. This study examined cerebral activation and functional connectivity in response to infant-directed speech (IDS) and adult-directed speech (ADS) in full-term neonates and preterm infants at term-equivalent age using 94-channel near-infrared spectroscopy. The results showed that compared with ADS, IDS increased activity in larger brain areas such as the bilateral frontotemporal, temporal, and temporoparietal regions, both in full-term and preterm infants. Preterm infants exhibited decreased activity in response to speech stimuli in the right temporal region compared with full-term infants, although the significance was low. Moreover, preterm infants exhibited increased interhemispheric connectivity compared with full-term controls, especially in the temporal and temporoparietal regions. These differences suggest that preterm infants may follow different developmental trajectories from those born at term owing to differences in intrauterine and extrauterine development.

Concepts: Pregnancy, Childbirth, Cerebral cortex, Cervix, Child development, Preterm birth, Infancy, Infant massage

48

To investigate whether the timing of probiotic milk intake before, during early or late pregnancy influences associations with preeclampsia and preterm delivery.

Concepts: Cohort study, Childbirth, Cohort, Epidemiology, Milk, Preterm birth

46

Widespread legalisation of marijuana raises safety concerns for its use in pregnancy. This study investigated the association of marijuana use prior to and during pregnancy with pregnancy outcomes in a prospective cohort of 5588 nulliparous women from the international SCOPE study. Women were assessed at 15±1 and 20±1 weeks' gestation. Cases [278 Preeclampsia, 470 gestational hypertension, 633 small-for-gestational-age, 236 spontaneous preterm births (SPTB), 143 gestational diabetes] were compared separately with 4114 non-cases. Although the numbers are small, continued maternal marijuana use at 20 weeks' gestation was associated with SPTB independent of cigarette smoking status [adjOR2.28 (95%CI:1.45-3.59)] and socioeconomic index (SEI) [adjOR2.17 (95%CI:1.41-3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks' gestation had a greater effect size [adjOR5.44 (95%CI 2.44-12.11)]. Our data indicate that increasing use of marijuana among young women of reproductive age is a major public health concern.

Concepts: Public health, Pregnancy, Childbirth, Hypertension, Smoking, Cigarette, Obstetrics, Preterm birth

32

There is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women.

Concepts: Childbirth, Magnesium sulfate, Preterm birth

30

To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk.

Concepts: Childbirth, Nutrition, Milk, Parenteral nutrition, Preterm birth

28

To test the hypothesis that preterm infants randomized to a low vs high O(2) saturation target range have a higher incidence of intermittent hypoxemia.

Concepts: Hypoxia, Preterm birth, Oxygen saturation, Hypoxemia

28

AIM: The aim of this study was to explore the effects of early oral ibuprofen administration on the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and define the association between serum ibuprofen levels and ductal closure. METHOD: Preterm infants with a gestational age of <28 weeks and/or birth weight of <1,000 g were randomized either to the intervention (ibuprofen prophylaxis) or control group. The intervention group received oral ibuprofen 10 mg/kg within 12-24 h after birth followed by 5 mg/kg at 24 and 48 h. Serum ibuprofen levels after the treatment were analyzed in the intervention group, and the incidence of hsPDA and complication rates were compared between two groups. RESULTS: Nineteen infants who received one course (three doses) of prophylactic ibuprofen in the intervention group and 17 infants in the control group who underwent an echocardiographic examination on the fourth day of life were analyzed. hsPDA was observed in five (26 %) infants in the intervention group and ten (58 %) infants in the control group (p = 0.09). In the intervention group two infants experienced gastrointestinal bleeding two infants had spontaneous intestinal perforation, and two infants developed acute kidney failure. Mean serum ibuprofen level was 28.7 ± 16.9 mg/L in the intervention group, and there was no correlation between ibuprofen level obtained on the fourth day and ductal closure. CONCLUSION: Oral ibuprofen prophylaxis reduces the rates of hsPDA even it is not statistically significant. The ductal closure rate did not correlate with serum ibuprofen levels. Due to high prevalence of adverse events observed, our data do not support the use of oral ibuprofen for prophylaxis of hsPDA.

Concepts: Renal failure, Fetus, Obstetrics, Ibuprofen, Patent ductus arteriosus, Ductus arteriosus, Preterm birth, Ligamentum arteriosum

27

Preterm birth places infants in an adverse environment that leads to abnormal brain development and cerebral injury through a poorly understood mechanism known to involve neuroinflammation. In this study, we integrate human and mouse molecular and neuroimaging data to investigate the role of microglia in preterm white matter damage. Using a mouse model where encephalopathy of prematurity is induced by systemic interleukin-1β administration, we undertake gene network analysis of the microglial transcriptomic response to injury, extend this by analysis of protein-protein interactions, transcription factors and human brain gene expression, and translate findings to living infants using imaging genomics. We show that DLG4 (PSD95) protein is synthesised by microglia in immature mouse and human, developmentally regulated, and modulated by inflammation; DLG4 is a hub protein in the microglial inflammatory response; and genetic variation in DLG4 is associated with structural differences in the preterm infant brain. DLG4 is thus apparently involved in brain development and impacts inter-individual susceptibility to injury after preterm birth.Inflammation mediated by microglia plays a key role in brain injury associated with preterm birth, but little is known about the microglial response in preterm infants. Here, the authors integrate molecular and imaging data from animal models and preterm infants, and find that microglial expression of DLG4 plays a role.

Concepts: DNA, Gene, Childbirth, Genetics, Gene expression, Transcription, Molecular biology, Preterm birth