Startseite Small for gestational age and extremely low birth weight infant outcomes
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Small for gestational age and extremely low birth weight infant outcomes

  • Elinor Charles , Katie A. Hunt , Christopher Harris , Ann Hickey und Anne Greenough EMAIL logo
Veröffentlicht/Copyright: 18. Oktober 2018
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Journal of Perinatal Medicine
Aus der Zeitschrift Journal of Perinatal Medicine Band 47 Heft 2

Abstract

Background

Small for gestational age (SGA) infants are less likely to develop respiratory distress syndrome (RDS), but more likely to develop bronchopulmonary dysplasia (BPD) and have a higher mortality. Our aim was to focus on outcomes of those with a birth weight less than or equal to 750 g.

Methods

The mortality, BPD severity, necrotising enterocolitis (NEC), home oxygen requirement and length of hospital stay were determined according to SGA status of all eligible infants in a 5-year period admitted within the first 24 h after birth.

Results

The outcomes of 84 infants were assessed, and 35 (42%) were SGA. The SGA infants were more mature (P<0.001), had a lower birth weight centile (P<0.001) and a greater proportion exposed to antenatal corticosteroids (P=0.022). Adjusted for gestational age (GA), there was no significant difference in mortality between the two groups (P=0.242), but a greater proportion of the SGA infants developed severe BPD (P=0.025). The SGA infants had a lower weight z-score at discharge (−3.64 vs. −1.66) (P=0.001), but a decrease in z-score from birth to discharge was observed in both groups (median −1.53 vs. −1.07, P=0.256).

Conclusion

Despite being more mature, the SGA infants had a similar mortality rate and a greater proportion developed severe BPD.

Keywords: bronchopulmonary dysplasia; extremely low birth weight; necrotising enterocolitis; small for gestational age

Introduction

Small for gestational age (SGA) infants have been shown to be less likely to develop respiratory distress syndrome (RDS), possibly due to intra-uterine stress leading to accelerated lung maturation [1]. Other outcomes, however, appear to be worse for those born SGA, that is, having a birth weight below the tenth centile for their gestational age (GA) and sex [1], [2], [3]. Amongst infants born at less than or equal to 36 weeks of gestation, the SGA infants had a higher mortality, a significantly higher risk of developing chronic lung disease and a longer hospital stay [1]. Furthermore, in infants born with a very low birth weight, the SGA group had increased risks of mortality and severe bronchopulmonary dysplasia (BPD) [2]. There has, however, been little focus on whether amongst infants with a birth weight less than or equal to 750 g, being born SGA influences mortality or morbidity. The aim of this study was to determine whether amongst such infants, those who were SGA had poorer outcomes than those who were born with a weight appropriate for their GA.

Materials and methods

A retrospective study of medical records and the BadgerNet Neonatal Electronic Patient Records at a tertiary neonatal intensive care unit (NICU) was undertaken. This study was undertaken as a clinical audit and as a consequence ethical approval was not required. All infants with a birth weight of 750 g or less, who were either born at or transferred to the hospital within the first 24 h after birth and admitted to the NICU for ongoing care between 2012 and 2016 were included in the study. Infants who died on the labour suite were not included.

Information extracted from the medical records included age at extubation, the occurrence of BPD, severe BPD and necrotising enterocolitis (NEC), whether the infants had had naso-jejunal feeding, their weight at birth and discharge and the change in birth weight centile from birth to discharge and the cause of any mortality. BPD was defined as an ongoing oxygen requirement at 28 days of age. Those infants requiring positive pressure support or ≥30% oxygen at 36 weeks post conceptional age were classified as having severe BPD [4]. NEC was diagnosed if there were both clinical signs (abdominal distension, abdominal discolouration, clinical instability, bilious aspirates and/or vomiting) and radiological abnormalities (pneumatosis intestinalis, gas in the hepato-biliary tract or a pneumoperitoneum) [5]. In addition, a surgical review had been undertaken and the infants had received a minimum of 5 days of treatment with antibiotics whilst being kept nil by mouth. Centiles and z-scores were calculated using UK World Health Organization (WHO) preterm reference ranges [6], and infants were divided into SGA and appropriate for gestational age (AGA) groups. SGA infants were defined as those below the tenth centile for sex and GA and AGA as those between the tenth and ninetieth centile.

Respiratory protocol

Infants of less than 32 weeks of GA who required intubation and ventilation in the delivery room were started on a peak inflation pressure (PIP) of 20–25 cm H2O, a positive end expiratory pressure (PEEP) of 4–5 cm H2O and a fraction of inspired oxygen (FiO2) of 0.21–0.30. They were given surfactant when stabilised. On transfer to the neonatal unit, they were ventilated on pressure-controlled time-cycled or assist-control ventilation using an SLE 5000 neonatal ventilator or an SLE 2000 infant ventilator (SLE, Croydon, UK). In the latter 2 years, volume-targeted ventilation was also used. All infants were ventilated with Cole’s shouldered endotracheal tubes which have been shown to have minimal or no leaks [7]. The supplementary oxygen was modified to achieve oxygen saturation levels between 92 and 95%. Infants who required a PIP exceeding 25 cm H2O were transferred to high frequency oscillation. Extubation was attempted when the FiO2 was ≤30% and the PIP had been reduced below 18 cm H2O. Caffeine was commenced in the first 24 h. The nurses recorded hourly on observation charts, the level of respiratory support required by the infant. Infants were considered for supplementary oxygen at home when they had reached full oral feeds at 3 hourly intervals, but still required supplementary oxygen. They were sent home on supplementary oxygen if they were stable and had suitable home conditions.

Feeding protocol

Our feeding policy followed the East of England guidelines with clinician’s discretion exercised on increasing feeds in line with the protocol [8]. In the study population, colostrum was encouraged for mouth care from day 1. Trophic feeds (<20 mL/kg/day) were started as soon as mother’s milk was available and clinical stability was achieved. If mother’s milk was not available and permission was given, donor milk was used. All of the infants in this study fulfilled the criteria for donor milk as they were born at a GA of less than 32 weeks. For infants whose mothers did not provide maternal milk, donor milk was continued for 14–21 days, when a transition to preterm formula was made to promote growth. Parenteral nutrition was commenced as early as possible post-delivery and standard bags were available out of hours. In infants with feed intolerance or dysmotility, concentrated parenteral nutrition at 50% of the total fluid intake was continued to ensure adequate calorie intake until growth and absorption were established. Using concentrated parenteral nutrition, up to 75% of calorie requirement can be given in 50% of the fluid volume. Fortifier was added to the breast milk at the consultant’s discretion, when infants achieved feed volumes of 150 mL/kg/day. Enteral feeds of 180 mL/kg/day of fortified maternal breast milk were aimed for in all infants. For formula-fed infants, volumes ranged from 150 mL/kg to 180 mL/kg depending on calorie content and growth. Energy dense term formula, e.g. infatrini, was considered for those approaching term corrected age and whose intake was limited by ongoing respiratory distress associated with BPD. Naso-jejunal feeding was considered for infants where feeding advancement was limited by either respiratory disease or gastro-oesophageal reflux. A multi-disciplinary nutrition team including a paediatric dietician and gastroenterologist reviewed all infants weekly to optimise nutrition and growth. Breastfeeding was actively encouraged by a dedicated NICU breast-feeding support worker; a specialised speech and language therapist was available.

Statistical analysis

The data were shown to be non-normally distributed and hence the Mann-Whitney U-test or chi-square (χ2) test was used as appropriate to assess whether differences in the demographics were statistically significant. Multiple linear regression or binary logistic regression as appropriate was used to adjust for differences in GA in the outcomes between the two groups. Statistical analysis was performed using IBM SPSS statistics version 24.

Results

Demographics

Thirty-five (42%) of the 84 infants in the study were SGA. The groups differed significantly at birth with regard to GA (P<0.001), birth weight (P=0.001) and birth weight z-score (P<0.001) (Table 1). A greater proportion of the SGA infants had mothers who had hypertension (P≤0.001), received antenatal steroids (P=0.022), had abnormal umbilical Doppler results and had a caesarean section delivery (P≤0.001). All of the infants were intubated and ventilated in the delivery suite and given surfactant.

Table 1:

Demographics according to SGA status.

SGA (n=35)AGA (n=49)P-value
Antenatal corticosteroids33 (94.3%)38 (78%)0.022
Maternal hypertension17 (48.6%)4 (8%)<0.001
Abnormal Dopplersa
 Normal8 (23%)33 (67%)<0.001
 Abnormal25 (71%)1 (2%)
Mode of delivery
 SVDb/instrumental11 (31%)45 (92%)<0.001
 Caesarean section24 (69%)4 (8%)
 Gestational age at birth, weeks26.9 (23.4–31.9)24.3 (22.3–26.7)<0.001
 Sex21 (60%)26 (53%)0.528
 Birth weight, g598 (450–732)662 (510–750)0.001
 z-Score at birth−2.22 (−3.64 to −1.38)−0.64 (−1.31 to +0.6)<0.001
 Birth centile1 (0.05–8)26 (10–73)<0.001
 Surfactant35 (100%)49 (100%)

  1. The results are demonstrated as median (range) or n (%). aData were not available for all infants. bSpontaneous vaginal delivery.

There were no significant differences in the mortality rate between the two groups (P=0.242). Eleven infants of the SGA group died. Their causes of death were extreme prematurity/hypoxic respiratory failure (n=7), respiratory failure secondary to BPD (n=2), pulmonary haemorrhage (n=1) and withdrawal of care following hypoxic brain injury after cardiac arrest (n=1). Fifteen infants of the AGA group died. Their causes of death were extreme prematurity/hypoxic respiratory failure (n=7), respiratory failure secondary to BPD (n=3), pulmonary haemorrhage (n=2), withdrawal of care following bilateral haemorrhagic parenchymal infarcts (n=1), Pseudomonas sepsis (n=1) and NEC (n=1). All infants who survived to 36 weeks corrected GA had BPD. A greater proportion of the SGA infants developed severe BPD (P=0.025) (Table 2), but there was no significant difference in the length of hospital stay or in the proportions of the two groups who required home oxygen (Table 2).

Table 2:

Mortality and respiratory morbidity according to SGA status.

SGA (n=35)AGA (n=49)Odds ratio or risk estimate for 95% confidence intervalsP-value adjusted for gestational age
Mortality11 (31%)15 (31.5%)0.75 (0.60–7.40)0.242
Age at death, days36 (1–536)14 (0–151)40 (−80 to 160)0.50
Severe BPDa17 (70.8%)22 (64.7%)2.39 (1.35–88.26)0.025
Length of hospital stay126.5 (63–404)130.5 (89–309)53 (−2.29 to 81.09)0.064
Home oxygen16 of 24 (67%)24 of 34 (71%)1.32 (0.56–24.73)0..173

  1. The results are expressed as median (range) or n (%). aOf all infants surviving to 36 weeks of gestation.

The SGA infants had a significantly lower weight z-score at discharge (P=0.001). A decrease in weight z-score from birth to discharge was observed in both groups and the change in weight z-score did not differ significantly between the two groups (P=0.256) (Table 3).

Table 3:

NICU course and discharge outcome.

SGA (n=35)AGA (n=49)Odds ratio or risk estimate (95% confidence interval)P-value adjusted for GA
NEC8/35 (23%)10/49 (20%)0.5 (0.1–2.5)0.349
Age at full enteral feeds, days53.5 (26–172)47.5 (11–184)38.2 (9.1–67.2)0.011
Required NJ feeding3/35 (8.6%)7/49 (14%)2.3 (0.28–18.7)0.443
Breastfeeding on discharge home6/24 (25%)12/34 (35%)1.6 (0.33–8.0)0.56
Any breast milk at discharge home10/24 (42%)20/34 (59%)2.5 (0.57–10.6)0.23
Length of hospital stay (days) in those surviving to discharge126.5 (63–404)130.5 (89–309)39.4 (−2.2–81)0.064
Weight z-score at discharge−3.64 (−4.93 to −1.73)−1.66 (−4.91 to 0.65)−1.5 (−2.4 to −0.67)0.001
Change in weight z-score from birth to discharge−1.53 (−4.01 to 0.54)−1.065 (−4.72 to 1.34)0.47 (−0.35 to 1.30)0.256

  1. Data are presented as n (%) or median (range). NJ, naso-jejunal.

Discussion

We have demonstrated that SGA infants were more likely to develop severe BPD than AGA infants (P=0.025), despite being more mature at birth and a greater proportion being exposed to antenatal corticosteroids. An increased risk of moderate to severe BPD (23% vs. 9%, respectively, P<0.001) [9] was found in a study of infants born before 32 weeks of gestation amongst those with antenatal growth restriction compared to those without [9]. Furthermore, amongst infants born before 28 weeks of gestation, fetal growth restriction was highly predictive of BPD after adjustment for other risk factors [10]. Our study uniquely reports an increased risk of severe BPD in SGA infants with a birth weight less than 750 g. Fetal growth restriction in animal models has been reported to result in structural changes to the lungs, that is, fewer and larger alveoli and a thickened blood-air barrier [11], [12]. Proposed mechanisms include malnutrition [12], [13] and increased exposure to proinflammatory cytokines both pre- and immediately postnatally [14], [15]. Nevertheless, we did not demonstrate that the SGA infants compared to the AGA infants were more likely to require “home oxygen” which may reflect their greater maturity at birth.

We found no significant difference in the mortality rate between the two groups, even when adjusted for GA. This finding is supported by a previous report of no significant difference in mortality between the SGA and AGA groups born between 26 and 28 weeks of GA [16], but they differed from our study population in that they had not been routinely exposed to antenatal steroids and postnatal surfactant. In contrast, in more mature infants, SGA has been frequently associated with an increased mortality [1], [2], [17].

The weight z-scores of infants born with a birth weight between 500 g and 749 g had been reported to fall by 1.10 from admission to discharge [18]. In 2013, half of the premature infants born weighing less than 1500 g in North American hospitals were discharged with a weight under the tenth centile for their age [19]. Low GA, low birth weight, the need for assisted ventilation on the first day after birth and the development of BPD have all been independently associated with poor growth [20], [21]. Although previous studies have suggested that SGA preterm infants experience a higher incidence of postnatal growth failure than AGA infants [22], we did not find this in our infants all who had a birth weight less than 750 g. Indeed, we did not find any significant difference in the changes in weight z-scores between AGA and SGA infants. We suggest our results may reflect a relatively aggressive nutritional policy.

Our study has strengths and some limitations. Previous studies have been criticised for failing to account for differences in GA and birth weight across cohorts and between comparison groups [1], [2]. We assessed the outcomes of all infants with a birth weight less than 750 g. Our SGA group had a significantly higher median GA than our AGA group; we, therefore, adjusted for GA when determining the impact of being SGA at birth on outcomes. Whilst previous studies have focused on very low birth weight infants (<1500 g) and premature infants (<36 weeks), this is the first study to look specifically at the effect of SGA in the extremely low birth weight infant, i.e. a birth weight less than 750 g.

In conclusion, amongst infants with a birth weight less than or equal to 750 g, those born SGA despite being on average 2 weeks more mature, had a similar mortality rate to the AGA infants. In addition, a greater proportion of the SGA infants had severe BPD and a similar length of stay to the AGA infants. These results should help to inform counselling of parents expecting an SGA, prematurely born infant.

Corresponding author: Professor Anne Greenough, Neonatal Intensive Care Centre, 4th Floor Golden Jubilee Wing, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, UK; MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, London, UK; Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; and National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK, Tel.: +0203 299 3037, Fax: +0203 299 8284

  1. Author contributions: AG and AH designed the study. EC collected the data. EC, KH, CH and AG analysed the data. All authors were involved in the production of the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, Grant Number: N/A. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2018-09-07
Accepted: 2018-09-25
Published Online: 2018-10-18
Published in Print: 2019-02-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Ultrasound Doppler waveform assessment: the story continues
  4. Review
  5. Association between increased antenatal vaginal pH and preterm birth rate: a systematic review
  6. Mini Review
  7. Update on uterine tachysystole
  8. Research Articles – Obstetrics
  9. First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study
  10. Emergency peripartal hysterectomy – a single-center analysis of the last 13 years at a tertiary perinatal care unit
  11. Efficacy and safety of misoprostol vaginal insert vs. oral misoprostol for induction of labor
  12. Vitamin A and β-carotene in pregnant and breastfeeding post-bariatric women in an urban population
  13. Effect of dual tocolysis with fenoterol and atosiban in human myometrium
  14. Antecedents of red cell transfusion in a large contemporary obstetric cohort
  15. Effect of n-3 long-chain polyunsaturated fatty acids supplementation in healthy mothers on DHA and EPA profiles in maternal and umbilical blood: a randomized controlled trial
  16. Research Articles – Fetus
  17. Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy
  18. Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction
  19. Doppler evaluation of the fetal pulmonary artery pressure
  20. Mechanisms of death in structurally normal stillbirths
  21. The diagnostic value of a detailed first trimester anomaly scan in fetuses with increased nuchal translucency thickness
  22. Research Articles – Newborn
  23. Small for gestational age and extremely low birth weight infant outcomes
  24. Does heart rate variability improve prediction of failed extubation in preterm infants?
https://doi.org/10.1515/jpm-2018-0295
Schlagwörter für diesen Artikel
bronchopulmonary dysplasia; extremely low birth weight; necrotising enterocolitis; small for gestational age

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Ultrasound Doppler waveform assessment: the story continues
  4. Review
  5. Association between increased antenatal vaginal pH and preterm birth rate: a systematic review
  6. Mini Review
  7. Update on uterine tachysystole
  8. Research Articles – Obstetrics
  9. First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study
  10. Emergency peripartal hysterectomy – a single-center analysis of the last 13 years at a tertiary perinatal care unit
  11. Efficacy and safety of misoprostol vaginal insert vs. oral misoprostol for induction of labor
  12. Vitamin A and β-carotene in pregnant and breastfeeding post-bariatric women in an urban population
  13. Effect of dual tocolysis with fenoterol and atosiban in human myometrium
  14. Antecedents of red cell transfusion in a large contemporary obstetric cohort
  15. Effect of n-3 long-chain polyunsaturated fatty acids supplementation in healthy mothers on DHA and EPA profiles in maternal and umbilical blood: a randomized controlled trial
  16. Research Articles – Fetus
  17. Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy
  18. Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction
  19. Doppler evaluation of the fetal pulmonary artery pressure
  20. Mechanisms of death in structurally normal stillbirths
  21. The diagnostic value of a detailed first trimester anomaly scan in fetuses with increased nuchal translucency thickness
  22. Research Articles – Newborn
  23. Small for gestational age and extremely low birth weight infant outcomes
  24. Does heart rate variability improve prediction of failed extubation in preterm infants?
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