Publications by authors named "Rosa Maria Cerbo"

15 Publications

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Prenatal and postnatal determinants in shaping offspring's microbiome in the first 1000 days: study protocol and preliminary results at one month of life.

Ital J Pediatr 2020 Apr 15;46(1):45. Epub 2020 Apr 15.

Dietetics and Clinical Nutrition Laboratory - Department of Public Health, Experimental and Forensic Medicine, University of Pavia, via Bassi 21, 27100, Pavia, Italy.

Background: Fetal programming during in utero life defines the set point of physiological and metabolic responses that lead into adulthood; events happening in "the first 1,000 days" (from conception to 2-years of age), play a role in the development of non-communicable diseases (NCDs). The infant gut microbiome is a highly dynamic organ, which is sensitive to maternal and environmental factors and is one of the elements driving intergenerational NCDs' transmission. The A.MA.MI (Alimentazione MAmma e bambino nei primi MIlle giorni) project aims at investigating the correlation between several factors, from conception to the first year of life, and infant gut microbiome composition. We described the study design of the A.MA.MI study and presented some preliminary results.

Methods: A.MA.MI is a longitudinal, prospective, observational study conducted on a group of mother-infant pairs (n = 60) attending the Neonatal Unit, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy). The study was planned to provide data collected at T0, T1, T2 and T3, respectively before discharge, 1,6 and 12 months after birth. Maternal and infant anthropometric measurements were assessed at each time. Other variables evaluated were: pre-pregnancy/gestational weight status (T0), maternal dietary habits/physical activity (T1-T3); infant medical history, type of feeding, antibiotics/probiotics/supplements use, environment exposures (e.g cigarette smoking, pets, environmental temperature) (T1-T3). Infant stool samples were planned to be collected at each time and analyzed using metagenomics 16S ribosomal RNA gene sequence-based methods.

Results: Birth mode (cesarean section vs. vaginal delivery) and maternal pre pregnancy BMI (BMI < 25 Kg/m vs. BMI ≥ 25 Kg/m), significant differences were found at genera and species levels (T0). Concerning type of feeding (breastfed vs. formula-fed), gut microbiota composition differed significantly at genus and species level (T1).

Conclusion: These preliminary and explorative results confirmed that pre-pregnancy, mode of delivery and infant factors likely impact infant microbiota composition at different levels.

Trial Registration: ClinicalTrials.gov identifier: NCT04122612.
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http://dx.doi.org/10.1186/s13052-020-0794-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158098PMC
April 2020

Survey of PDA management in very low birth weight infants across Italy.

Ital J Pediatr 2020 Feb 14;46(1):22. Epub 2020 Feb 14.

Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria S Maria della Misericordia, Udine, Italy.

Background: The optimal management of PDA in very low birth weight (VLBW) infants is still controversial. Aim of our study was to investigate the management of PDA in the Italian neonatal intensive care units (NICU).

Methods: We conducted an on-line survey study from June to September 2017. A 50-items questionnaire was developed by the Italian Neonatal Cardiology Study Group and was sent to Italian NICUs.

Results: The overall response rate was 72%. Diagnosis of PDA was done by neonatologists, cardiologists or both (62, 12 and 28% respectively). PDA significance was assessed by a comprehensive approach in all centers, although we found a heterogeneous combination of parameters and cut-offs used. None used prophylactic treatment. 19% of centers treated PDA in the first 24 h, 60% after the first 24 h, following screening echocardiography or clinical symptoms, 18% after the first 72 h and 2% after the first week. In the first course of treatment ibuprofen, indomethacin and paracetamol were used in 87, 6 and 7% of centers respectively. Median of surgical ligation was 3% (1-6%).

Conclusions: Significant variations exist in the management of PDA in Italy. Conservative strategy and targeted treatment to infants older than 24 h with echocardiographic signs of hemodynamic significance seemed to be the most adopted approach.
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http://dx.doi.org/10.1186/s13052-020-0773-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023762PMC
February 2020

Neonatologist performed echocardiography (NPE) in Italian neonatal intensive care units: a national survey.

Ital J Pediatr 2019 Oct 22;45(1):131. Epub 2019 Oct 22.

Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria S Maria della Misericordia, Udine, Italy.

Background: Neonatologist performed echocardiography (NPE) has increasingly been used to assess the hemodynamic status in neonates. Aim of this survey was to investigate the utilization of NPE in Italian neonatal intensive care units (NICUs).

Methods: We conducted an on-line survey from June to September 2017. A questionnaire was developed by the Italian neonatal cardiology study group and was sent to each Italian NICU.

Results: The response rate was 77%. In 94% of Italian NICUs functional echocardiography was used by neonatologists, cardiologists or both (57, 15 and 28% respectively). All the respondents used NPE in neonates with patent ductus arteriosus and persistent pulmonary hypertension, 93% in neonates with hypotension or shock, 85% in neonates with perinatal asphyxia, 78% in suspicion of cardiac tamponade, and 73% for line positioning. In 30% of center, there was no NPE protocol. Structural echocardiography in stable and critically ill neonates was performed exclusively by neonatologists in 46 and 36% of center respectively.

Conclusions: NPE is widely used in Italian NICUs by neonatologists. Structural echocardiography is frequently performed by neonatologists. Institutional protocols for NPE are lacking. There is an urgent need of a formal training process and accreditation to standardize the use of NPE.
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http://dx.doi.org/10.1186/s13052-019-0721-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805655PMC
October 2019

Inherited human IRAK-1 deficiency selectively impairs TLR signaling in fibroblasts.

Proc Natl Acad Sci U S A 2017 01 9;114(4):E514-E523. Epub 2017 Jan 9.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, 75015 Paris, France;

Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear. We describe here a boy with X-linked MECP2 deficiency-related syndrome due to a large de novo Xq28 chromosomal deletion encompassing both MECP2 and IRAK1 Like many boys with MECP2 null mutations, this child died very early, at the age of 7 mo. Unlike most IRAK-4- or MyD88-deficient patients, he did not suffer from invasive bacterial diseases during his short life. The IRAK-1 protein was completely absent from the patient's fibroblasts, which responded very poorly to all TLR2/6 (PAMCSK, LTA, FSL-1), TLR1/2 (PAMCSK), and TLR4 (LPS, MPLA) agonists tested but had almost unimpaired responses to IL-1β. By contrast, the patient's peripheral blood mononuclear cells responded normally to all TLR1/2, TLR2/6, TLR4, TLR7, and TLR8 (R848) agonists tested, and to IL-1β. The death of this child precluded long-term evaluations of the clinical consequences of inherited IRAK-1 deficiency. However, these findings suggest that human IRAK-1 is essential downstream from TLRs but not IL-1Rs in fibroblasts, whereas it plays a redundant role downstream from both TLRs and IL-1Rs in leukocytes.
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http://dx.doi.org/10.1073/pnas.1620139114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278481PMC
January 2017

Near-Infrared Spectroscopy Monitoring, Superior Vena Cava Flow, and Neurodevelopmental Outcome at 2 years in a Cohort of Very Low-Birth-Weight Infants.

Am J Perinatol 2016 09 7;33(11):1093-8. Epub 2016 Sep 7.

Neonatal Intensive Care Unit, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.

Objective We aimed at assessing the association between superior vena cava flow (SVCf), regional (cerebral) tissue oxygen saturation (rSO2), and cerebral fractional oxygen extraction (CFOE) during the first 48 hours of life and 2-years neurodevelopmental outcome of very low-birth-weight infants (VLBW). Methods We prospectively studied 60 VLBW infants admitted to our neonatal intensive care unit; rSO2 was continuously monitored with near-infrared spectroscopy during the first 48 hours of life, SVCf was measured at 4 to 6, 12, 24, and 48 hours, and CFOE was calculated. Neurodevelopmental outcome was assessed at 24 months corrected age. Results The mean gestational age at birth was 27.9 weeks (standard deviation: 2.4); 8 infants died in the first 3 months of life, 6 were lost to follow-up, 46 survived and were followed up. At 24 months, 6 (13%) and 7 (15.2%) infants developed minor and major sequelae, respectively. Infants who died had higher CFOE (p < 0.001) and lower SVCf (p < 0.001) than infants surviving with sequelae. In turn, these had higher SVCf between 24 and 48 hours than those without sequelae (p < 0.001). Conclusion SVCf, rSO2, and CFOE patterns in the first days of life suggest cerebral hyperperfusion, related to loss of autoregulation and/or use of inotropic drugs, as a potential mechanism of cerebral injury.
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http://dx.doi.org/10.1055/s-0036-1586103DOI Listing
September 2016

Cerebral Oxygenation, Superior Vena Cava Flow, Severe Intraventricular Hemorrhage and Mortality in 60 Very Low Birth Weight Infants.

Neonatology 2015 25;108(4):246-52. Epub 2015 Aug 25.

Neonatal Intensive Care Unit, Scientific Direction, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.

Background: Brain vulnerability in the critically ill preterm newborn may be related to the burden of cerebral hypoxygenation and hypoperfusion during the immediate postnatal period.

Objective: We determined the association between adverse outcomes [death or high grade intraventricular hemorrhage (IVH)] and continuous cerebral tissue oxygen saturation (rSO2), superior vena cava flow (SVCf) and cerebral fractional oxygen extraction (CFOE) in very low birth weight (VLBW) infants during the first 48 h of life.

Methods: We studied a prospective cohort of 60 VLBW infants admitted to our neonatal intensive care unit within the first 6 h of life between March 2010 and June 2012. rSO2 (expressed as a number of summary measures) was continuously monitored with near-infrared spectroscopy (INVOS 5100 Somanetic) during the first 48 h of life, SCVf was measured at 4-6, 12, 24 and 48 h after birth, and CFOE was calculated.

Results: The mean gestational age was 27.9 (SD 2.39); 8 infants died (13.3%) and 7 developed IVH grade III-IV: 1 in the alive group and 6 in the deceased group (p < 0.001). The odds ratio for death was 1.08 (95% CI: 1.015-1.15, p = 0.016) for each 10 periods of rSO2 values <40% in the first 48 h, and 4.2 (95% CI: 1.27-14.05, p = 0.019) for SVCf values <40 ml/kg/min. Among alive babies, mean CFOE decreased at 24, 36 and 48 h; among deceased babies it did not (p < 0.001). In the multivariate analyses, these results retained significance.

Conclusions: Both rSO2 ≤40% and SVCf <40 ml/kg/min independently increase the risk of death. The trend in CFOE supports the ischemic-hypoperfusion hypothesis as a mechanism for cerebral damage.
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http://dx.doi.org/10.1159/000438452DOI Listing
August 2016

Genomic alterations in human umbilical cord-derived mesenchymal stromal cells call for stringent quality control before any possible therapeutic approach.

Cytotherapy 2013 Nov;15(11):1362-73

Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico "San Matteo," Pavia, Italy; Laboratory of Neonatal Immunology, Fondazione IRCCS Policlinico "San Matteo," Pavia, Italy. Electronic address:

Background Aims: The umbilical cord (UC) is a promising source of mesenchymal stromal cells (MSCs). UC-MSCs display very similar in vitro characteristics to bone marrow-MSCs and could represent a valuable alternative for cell-based therapies. However, it is still unclear whether UC-MSCs are prone or not to the acquisition of genomic imbalances during in vitro expansion.

Methods: With the use of array-comparative genomic hybridization, we compared copy number variations of early (P2-P3) and late (>P5) passages of in vitro-expanded UC-MSCs.

Results: In two of 11 long-term UC-MSCs cultures, we observed the appearance of clones carrying genomic imbalances, which generated genetic mosaicism at intermediate passages. Although still able to reach the senescence phase, the cells carrying the genomic imbalance acquired a proliferative advantage, as demonstrated by the increase in frequency during long-term culture.

Conclusions: Altogether, our results suggest that UC-MSC-based clinical protocols should be designed with caution; their clinical use should be preceded by array-comparative genomic hybridization screening for the acquisition of genomic imbalances during in vitro expansion.
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http://dx.doi.org/10.1016/j.jcyt.2013.06.006DOI Listing
November 2013

Global perfusion assessment and tissue oxygen saturation in preterm infants: where are we?

Early Hum Dev 2013 Jun;89 Suppl 1:S44-6

Neonatal Intensive Care Unit, Fondazione IRCCS-Policlinico San Matteo, Pavia, Italy.

Near infrared spectroscopy (NIRS) monitoring is a new challenge for clinicians who deal with early detection of dangerous hypoperfusion in the brain, as well as in splanchnic and renal districts in critically ill preterm infants. Previous studies performed on infants and children with congenital heart disease, demonstrated the efficacy of this non-invasive method in managing hypoperfusive states pre, post and during cardiac surgery. Its use has improved post surgery outcome. NIRS monitoring has been used also to assess therapeutic intervention utility. Early identification of silent hypoperfusion has made NIRS use in preterm infants very interesting for neonatologists, especially where other techniques have failed. In this work, literature on this topic has been carefully examined, particularly the "two site NIRS" use in preterm infants, to evaluate how regional splanchnic oxygen saturation changes, both in physiological events, such as enteral feeding and in hemodynamic disorders, that occur in patients with significant patent ductus and in hypoperfusive states that lead to necrotizing enterocolitis.
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http://dx.doi.org/10.1016/S0378-3782(13)70014-8DOI Listing
June 2013

A newborn with double-outlet right ventricle and aortopulmonary window associated with maternal phenylketonuria: a first case report.

Acta Paediatr 2011 Mar 2;100(3):318. Epub 2010 Nov 2.

Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

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http://dx.doi.org/10.1111/j.1651-2227.2010.02066.xDOI Listing
March 2011

BNP concentrations and cardiovascular adaptation in preterm and fullterm newborn infants.

Early Hum Dev 2010 May 20;86(5):295-8. Epub 2010 May 20.

Pediatric Cardiology, Department of Paediatrics, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.

To evaluate and compare cardiovascular adaptation of 36 preterm and 34 fullterm newborns, we analyzed BNP concentration and echocardiographic parameters at day 3 of life and at day 28 (+/-2). On day 3 BNP concentrations (pg/ml) resulted higher in PDA preterm group (n=11; 125, IQR 56.1-301) than preterm without PDA (n=25; 25.5 IQR 10.9-49; p<0.001) than fullterms (n=34; 55.1 IQR 23.6-82.7; p=0.013). No difference resulted in all groups at 28days (respectively: 12.7 IQR 4.9-23.8; 15.6 IQR 10-22; 8.9 IQR 5.6-20.6). Because of the newborns' growth, all echocardiographic parameters increased with linear relationship with body weight. On day 3 BNP concentration and echocardiographic parameters were not correlated besides LA/AO in preterms with PDA (p=0.0015). On day 28, BNP was significantly correlated with mVTI (p=0.019), M (p=0.007) and LA (p=0.005) in fullterms and only with LA (p=0.007) in preterms. In conclusion, BNP concentrations and echocardiographic measures confirm that preterm, and fullterm newborns conduct themselves in a similar manner during the transition from foetal to post-natal circulation, reaching low levels at a month of life. The presence of PDA during first days of life has no significant impact in this adaptation. LA is the echocardiographic parameter mostly related to BNP concentration in the newborns.
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http://dx.doi.org/10.1016/j.earlhumdev.2010.04.003DOI Listing
May 2010

Persistent pulmonary hypertension of the newborn refractory to inhaled nitric oxide-treated with milrinone: a case report.

Turk J Pediatr 2010 Jan-Feb;52(1):78-80

Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Current therapy of persistent pulmonary hypertension of the newborn (PPHN) consists of optimal ventilation, hemodynamic support and selective vasodilatation with inhaled nitric oxide (iNO). We present herein a case of PPHN non-responsive to iNO but treated successfully with a combination of iNO and intravenous milrinone, a phosphodiesterase III inhibitor. This case suggests that the drug may be a useful adjunctive treatment in the management of PPHN.
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May 2010

From apneic spells to the development of hypertensive hydrocephalus: a case report of homocystinuria with early onset.

J Child Neurol 2010 Mar 9;25(3):368-70. Epub 2009 Jun 9.

Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of homocysteine in the serum and an increased excretion of homocysteine in the urine. The infantile form is severe: the main clinical findings are neurologic signs, associated with hematological signs and bone alterations. Immediate restoration of plasma amino acids is the primary goal and early diagnosis is crucial not to delay the onset of possible treatment. We report a case of homocystinuria with early onset: an initial symptomatology was undervalued by the pediatrician with a delay in diagnosis. Despite the therapy, the patient developed tetraventricular hydrocephalus requiring ventricular drainage. In conclusion, we want to remember the necessity to perform a complete metabolic workup in a patient with clinical manifestations suggestive for homocystinuria, and the importance of early recognition of the signs and symptoms of hypertensive hydrocephalus, a possible complication of this condition.
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http://dx.doi.org/10.1177/0883073809336877DOI Listing
March 2010

Cerebral arteriovenous shunts regression in two preterm newborns with heart failure in utero.

Am J Perinatol 2009 Oct 23;26(9):637-9. Epub 2009 Apr 23.

Neonatal Intensive Care Unit, Fondazione IRCCS San Matteo, Pavia, Italy.

In this report, the cases of two newborn infants with cerebral arteriovenous shunts and heart failure in utero are presented. Different from the malformations of the vein of Galen, which usually generate a progressive and lethal heart failure after birth, our cases show heart failure resolution after birth, together with cerebral vascular shunt disappearance. Therefore, we hypothesized that the opening of arteriovenous shunts was a secondary modification due to the intrauterine heart failure. From our cases, it appears that, despite the dramatic echographic appearance, generalized cerebral venous dilatation can resolve spontaneously without sequelae.
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http://dx.doi.org/10.1055/s-0029-1220795DOI Listing
October 2009

Correlation between cord blood, perinatal BNP values and echocardiographic parameters in healthy Italian newborns.

Early Hum Dev 2009 Jan 27;85(1):13-7. Epub 2008 Jun 27.

Pediatric Cardiology, Department of Paediatrics, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

We evaluated the correlation between brain natriuretic peptide (BNP) in umbilical cord blood after normal pregnancy, in blood samples of twenty-nine Italian healthy newborns and paired echocardiographic parameters. Plasma BNP was evaluated in UCB (T0) and in blood on day 3 (T1), 30 (T2) of life. Echocardiographic parameters were recorded at T1 and T2. Median of BNP concentrations in cord blood was 8.6 pg/ml. Median BNP concentrations on T1 was 59.2 pg/ml, on T2 was 8.7 pg/ml. Significantly higher BNP concentrations were reported on T1 than T0 and T2 (p<0.0001), while no significant difference resulted between T0 and T2. Plasma BNP at T2 was significantly correlated with mVTI (p=0.006), E wave (p=0.004), LA (p=0.047), LVPW (p=0.004), M (p=0.025). No correlation was found with SF% and E/A. Our results confirm that in healthy and term neonates the cord blood BNP concentrations are low. On T1 BNP values are high with wide ranges because of physiological adjustment to postnatal circulation. When echocardiographic parameters are in normal ranges, BNP concentrations return to low levels on day 30. In healthy newborns left ventricular filling, LA size and M seem to influence BNP levels rather than left ventricular systolic and diastolic function.
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http://dx.doi.org/10.1016/j.earlhumdev.2008.05.008DOI Listing
January 2009

Two-year infant neurodevelopmental outcome after single or multiple antenatal courses of corticosteroids to prevent complications of prematurity.

Am J Obstet Gynecol 2004 Jul;191(1):217-24

Department of Obstetrics and Gynecology, University of Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy.

Objective: This study was undertaken to evaluate the effect of exposure to multiple antenatal steroid courses on short-term neonatal morbidity and 2-year infant neurodevelopmental outcome.

Study Design: This was a prospective observational study of 201 preterm singleton infants who received 1 or more courses of corticosteroids to prevent complications of prematurity and were delivered between 24 and 34 weeks' gestation at a single institution. Neurodevelopmental outcome of the infants was evaluated at 2 years corrected age. Logistic regression analysis was used to perform multivariate analyses of associations and trends.

Results: One hundred thirty-eight subjects (68.7%) received at least 1 complete course of betamethasone, whereas 63 (31.3%) patients were treated with dexamethasone. The prevalence of multiple steroid doses exposure was 26.8% (37/138) in betamethasone and 52.4% (33/63) in dexamethasone group. The prevalence of infant leukomalacia, including both prolonged echogenicity and cystic leukomalacia, was 25.9% (34/131) after a complete corticosteroid course, 40% (6/15) after 1, 42.3% (12/28) after 2, and 44.4% (12/27) after more than 2 additional courses, respectively (adjusted P for trend=.011). In the same categories of steroid exposure, the corresponding prevalences of 2-year infant neurodevelopmental abnormalities were 18% (20/111), 21.4% (3/14), 29.2% (7/24), and 34.8% (8/23), respectively (adjusted P for trend=.038). Multivariate study of first grade interaction suggested that the risk of leukomalacia and 2-year infant neurodevelopmental abnormalities associated with multiple doses exposure was confined to dexamethasone. In fact, compared with betamethasone, exposure to multiple doses of dexamethasone was associated with an increased risk of leukomalacia (19/33 compared with 11/37; odds ratio [OR]=3.21, 95% CI=1.07-9.77) and overall 2-year infant neurodevelopmental abnormalities (12/28 compared with 6/35; OR=3.63, 95% CI=1.03-13.58).

Conclusion: In this study, multiple antenatal courses of dexamethasone but not betamethasone were associated with an increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalities.
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http://dx.doi.org/10.1016/j.ajog.2003.12.023DOI Listing
July 2004