Association of intrauterine growth restriction and low birth weight with acute kidney injury in preterm neonates.

BACKGROUND: Preterm birth alters nephrogenesis and reduces the total nephron number. Intrauterine growth restriction (IUGR) seems to worsen nephron loss, but only a few studies have investigated its role in neonatal kidney impairment. We investigated whether IUGR, defined as reduced estimated fetal growth and/or placental flow alterations and low birth weight z-score, increases the risk of developing acute kidney injury (AKI) in very preterm infants. METHODS: We performed a retrospective study including infants born with a birth weight (BW) ≤ 1500 g and/or gestational age (GA) ≤ 32 weeks admitted to our center between January 2016 and December 2021. Neonatal AKI was defined according to the neonatal KDIGO classification based on the decline of urine output and/or creatinine elevation. We used multivariable linear regressions to verify the association between AKI and GA, BW z-score, IUGR definition, and hemodynamically significant patent ductus arteriosus (PDA). RESULTS: We included 282 infants in the analysis, with a median (IQR) GA = 29.4 (27.4, 31.3) weeks, BW = 1150 (870, 1360) g, and BW z-score = - 0.57 (- 1.64, 0.25). AKI was diagnosed in 36 (13%) patients, and 58 (21%) had PDA. AKI was significantly associated with BW z-score (beta (std. error) = - 0.08 (0.03), p = 0.008) and severe IUGR (beta (std. error) = 0.21 (0.08), p = 0.009), after adjusting for GA and PDA. CONCLUSIONS: Our data suggest that low BW z-score and IUGR could represent adjunctive risk factors for kidney impairment in preterm babies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Selective IUGR in dichorionic twins: what can Doppler assessment and growth discordancy say about neonatal outcomes?

OBJECTIVE: The aim of the present study was to assess, in a population of dichorionic twin pregnancies with selective growth restriction, the effect of inter-twin differences by use of Doppler velocimetry and fetal growth discordancy on perinatal outcomes. METHODS: This was a retrospective study including dichorionic twin pregnancies from January 2008 to December 2015 at the Department of Obstetrics and Gynecology of Fondazione MBBM. Only dichorionic twin pregnancies affected by selective intrauterine growth restriction (IUGR) delivering at ≥24 weeks were included in the study. RESULTS: We found that twin pregnancies with inter-twin estimated fetal weight (EFW) discordance ≥15% were significantly associated with a higher risk of preterm delivery before 32 (P=0.004) and 34 weeks (P=0.04). Similarly, twin pregnancies with inter-twin abdominal circumference (AC) discordance ≥30° centiles were associated with a higher rate of neonatal intensive care unit (NICU) admission (P=0.02), neonatal resuscitation (P=0.02) and adverse neonatal composite outcome (P=0.04). Of interest, when comparing twin pregnancies according to Doppler study, growth restricted twins had a higher rate of composite neonatal outcome and in multivariate analysis, an abnormal Doppler was an independent risk factor for this outcome. CONCLUSIONS: Our study associated growth discrepancy with specific pregnancy outcomes, according to defined cut-offs. In addition, we demonstrated that an abnormal umbilical artery Doppler is independently associated with a composite neonatal adverse outcome in growth restricted fetuses.

Monitoring Doppler patterns and clinical parameters may predict feeding tolerance in intrauterine growth-restricted infants.

AIM: To detect predictors of feeding tolerance in intrauterine growth restriction (IUGR) infants with or without brain-sparing effect (BS). METHODS: We conducted a case-control study in 70 IUGR infants (35 IUGR with BS, matched for gestational age with 35 IUGR infants with no BS). BS was classified as pulsatility index (PI) ratio [umbilical artery (UAPI) to middle cerebral artery (MCAPI) (U/C ratio)] > 1. Clinical parameters of feeding tolerance - days to achieve full enteral feeding (FEF) - were compared between the IUGR with BS and IUGR without BS infants. Age at the start of minimal enteral feeding (MEF) was analysed. RESULTS: Achievement of FEF was significantly shorter in IUGR infants without BS than in IUGR with BS. IUGR with BS started MEF later than IUGR without BS infants. Significant correlation of MEF and FEF with UA PI, U/C ratio and CRIB score was found. Multiple linear regression analysis showed significant correlations with CRIB score and caffeine administration (MEF only), and sepsis (FEF only) and U/C ratio (for both). CONCLUSION: Impaired gut function can be early detected by monitoring Doppler patterns and clinical parameters.

Fibroids-related complications in pregnancy: a twelve-year long experience at a maternal-fetal medicine referral center.

BACKGROUND: Uterine fibroids are the most frequent female benign tumor, which can cause complications during pregnancy, mainly pain. Differential diagnosis may be challenging and a standardized management approach is lacking. We aim to propose an algorithm for the differential diagnosis of pain during pregnancy and for management of fibroid-related pain. METHODS: A retrospective cohort study of all pregnant women admitted to our center for complications related to fibroids between 2008 and 2019. Data regarding clinical examination, laboratory results, imaging parameters, as well as perinatal outcomes, were collected and assessed (Fisher's Exact Test). RESULTS: Twenty-four pregnant patients were admitted for fibroid-related complications. Six patients were admitted more than one times, for a total of 34 admissions. The main cause of hospital admission was pain (N.=33, 94.1%), which was successfully managed with acetaminophen and/or ketoprofen in 91.2%. In two cases, conservative management failed and a surgical approach was undertaken. Most women (N.=20, 90.9%) delivered at term, with a cesarean delivery and post-partum hemorrhage rate of 22.7%. All newborns had normal APGAR score, umbilical artery pH and birth weight. CONCLUSIONS: Pain is the most common complication of fibroids during pregnancy. Accurate differential diagnosis and adequate management are pivotal to ensure good perinatal outcomes.

Infants weighing <1500 g: better born too small or too soon?

OBJECTIVE: To evaluate the influence of intrauterine growth on intact neurological outcome at 12 to 24 months in a cohort of infants weighing <1500 g at birth. STUDY DESIGN: This retrospective study was conducted in the Department of Obstetrics and Gynecology, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. Perinatal variables were correlated with occurrence of composite adverse outcome, including neonatal death or adverse neurodevelopmental outcome (ANDO), at 12 to 24 months' follow-up, in 240 consecutive very low-birth-weight (VLBW) neonates prenatally classified as growth restricted (IUGR; n = 100) or appropriate for gestational age (n = 140). RESULTS: Among the 214 surviving neonates, neurological follow-up was available in 163. ANDO was present in 46 children (28%). At multivariate analysis, only gestational age at delivery was independently related to the composite outcome (p < 0.001, odds ratio = 0.69, 95% confidence interval 0.59, 0.81), whereas diagnosis of IUGR was not. CONCLUSION: Only gestational age at delivery was significantly associated with composite adverse outcome in VLBW preterm infants.

Placental growth factor as a predictive marker of preeclampsia - PREBIO study - PREeclampsia BIOchemical study.

INTRODUCTION: To evaluate the clinical utility of placental growth factor (PlGF) for the prediction of preeclampsia (PE). MATERIALS AND METHODS: This prospective cohort study included women divided into three groups: (1) pregnancies without preconceptional risk of developing PE; (2) pregnancies with a preconceptional and/or current risk of developing PE; (3) PE-complicated pregnancies (control group). Blood samples were collected every 4-5 weeks or during hospitalization from early second trimester until delivery in the group 1 and 2, at the diagnosis of PE in the group 3. Plasma levels of PlGF were measured using The Triage PlGF test (Alere) and considered pathological under the 5th centile for gestational age. Sensitivity (Sn), specificity (Sp), positive and negative predictive value (PPV, NPV) were calculated. RESULTS: In group 1, 30% of women (3/10) had pathological test but none of them developed PE (Sp 70%, NPV 100%). In group 2 (n = 75), none of the patients with normal test developed PE (0/24), while 39% of women with PlGF < 5th centile (20/51) developed PE (Sn 100%, Sp 44%, PPV 39%, NPV 100%). In group 3 (n = 11) all women except one had a pathological PlGF test (Sn 90%, PPV 100%). CONCLUSIONS: Our data support recent studies which identify PlGF as a biochemical marker not only of PE, but also of placental dysfunction. In fact, it is useful for ruling out PE in women at risk because of the high Sn and high NPV: a normal PlGF is related with a positive pregnancy outcome. Therefore, the measurement of this biomarker would simplify PE clinical management and would reduce costs.

Splenic artery aneurysm in obstetrical patients: A series of four cases with different clinical presentation and outcome.

OBJECTIVE: To describe four consecutive cases of splenic artery aneurysm (SAA) with different clinical patterns of presentation among obstetrical patients. METHODS: A series of four cases of SAA diagnosed in pregnant or postpartum women at our University center between January 1998 and December 2020. Clinical and radiologic data were retrospectively obtained by reviewing paper and electronic medical records after acquiring patient's consent. RESULTS: One case was completely asymptomatic and incidentally identified at the beginning of pregnancy, thus allowing for multidisciplinary treatment. The other three cases were unknown: two manifested with maternal collapse due to aneurysm rupture in the third trimester of gestation, whereas one presented with acute abdominal pain during the postpartum period and was successfully managed before rupture occurred. CONCLUSION: Although extremely rare, SAA rupture in obstetrical patients can be associated with dramatic consequences. Early suspicion and prompt intervention are essential to avoid fatal outcomes, so promotion of knowledge of all the potential clinical patterns of presentation of SAA rupture among obstetrical patients is mandatory.

Factors affecting survival in infants weighing 750 g or less.

OBJECTIVE: To assess which factors independently affect survival in infants weighing 750g or less. STUDY DESIGN: We reviewed the obstetric, neonatal, and placental pathology information of all non-malformed neonates with birth weight of 750g or less from January 1998 to December 2002. Logistic regression analysis was used to control for the effect of confounding variables. A P<0.05 was considered significant. RESULTS: Fifty nine neonates fulfilled the inclusion criteria; 30 (51%) survived the perinatal period. Surviving neonates were more frequently born after steroid administration (P=0.03) and from indicated delivery (P=0.01), had greater birth weight (P=0.001), gestational age at delivery (P<0.001), and 5-min Apgar scores of 7 or more (P=0.04) than those who died. There were no significant differences in placental pathology between survivors and neonates who died. Stepwise logistic regression analysis showed that gestational age (P=0.01), birth weight (P=0.004), female sex (P=0.03), 5-min Apgar score (0.026), and steroid administration (P=0.04) were independent predictors of survival. Cumulatively these five predictors explained 69% of neonatal survival. CONCLUSIONS: The predictors of survival among micropremies are the same as those reported for older preterm neonates. The type of preterm delivery (spontaneous versus indicated) and placental pathology do not independently affect survival.

Obstetric cholestasis: outcome with active management.

OBJECTIVE: Conservative management of intrahepatic obstetric cholestasis is associated with a high stillbirth rate despite monitoring of fetal well-being with non-stress test and amniotic fluid volume assessment. Most cases of stillbirth are associated with meconium passage. We prospectively evaluated the effect of a management protocol inclusive of surveillance for presence of meconium and induction of labor at 37 weeks. STUDY DESIGN: Between January 1989 and December 1997, all women with obstetric cholestasis underwent transcervical amnioscopy after 36 weeks for assessment of amniotic fluid color, in addition to standard monitoring of fetal well-being (semi-weekly non-stress test and amniotic fluid volume determinations). Amniocentesis for fetal lung maturity and amniotic fluid color assessment was performed before 36 weeks in severe cases. Labor was induced at 37 weeks or earlier in the presence of non-reassuring fetal testing, meconium, or severe maternal symptoms unresponsive to therapy with mature fetal lungs. The obstetric outcome of the group with cholestasis was compared with that of the general obstetric population at our Institution during the study period. The rate of fetal death in the study group was compared with that of series published within the last 20 years, which used expectancy and conventional monitoring of fetal well-being. Statistical analysis utilized Fisher's exact test, Chi-square, and Student's t-test with P value <0.05 or an odds ratio (OR) with 95% confidence interval (CI) not inclusive of the unity considered significant. RESULTS: Obstetric cholestasis was diagnosed in 206/20,815 pregnant women (1%) at a median gestational age of 34 weeks (range 20-40). Delivery was prompted by non-reassuring fetal testing in four cases (2%). Meconium passage was documented in 33 cases (16%), in 11 of which before onset of labor and in 10 before 37 weeks. The rate of meconium passage before 37 weeks (17.9 versus 2.9%, OR=7.3; 95% CI 3.3, 16.0) was significantly higher in obstetric cholestasis than in the general obstetric population, whereas the cesarean section rate was similar in the two groups (15.1 versus 16.0%, OR=0.9; 95% CI 0.6, 1.4). The fetal death rate was significantly lower in the group managed with the current strategy than in the published series of obstetric cholestasis (0/218 versus 14/888, P=0.045). CONCLUSION: In pregnancies complicated by obstetric cholestasis, a protocol inclusive of search for meconium and elective delivery at 37 weeks, in addition to standard monitoring of fetal well-being, can significantly reduce the stillbirth rate without increasing the cesarean delivery rate.

Prediction of superimposed preeclampsia using uterine artery Doppler velocimetry in women with chronic hypertension.

OBJECTIVE: To assess the role of uterine artery (UtA) Doppler to predict superimposed preeclampsia in women with chronic hypertension. METHODS: In a cohort of 182 women with chronic hypertension, UtA Doppler studies were performed before 25 weeks (mean 19.7 +/- 2.1 weeks) and repeated later in pregnancy (mean 28.5 +/- 3.7 weeks). RESULTS: The incidence of preeclampsia was 13% (24/182). Rates of preeclampsia increased with advancing gestation of abnormal UtA Doppler: 7% when UtA Doppler were normal at early exam, 18% when abnormal at early exam, and 28% when abnormal at late exam (Chi-square for trend: P < 0.001). The rate of preeclampsia among 40 women with abnormal early but normal late UtA Doppler was similar to that of women with normal findings at early exam (8 vs 7%; P = 1.00). Logistic regression analysis showed that the ability of UtA Doppler to predict preeclampsia was independent from other variables [Odds Ratio (OR) 7.1, 95% Confidence Interval (CI) 2.6-18.9). Receiver operating characteristic (ROC) curve identified a UtA value of 0.58 as the optimal threshold for the prediction of preeclampsia. CONCLUSION: The later in pregnancy the abnormal UtA Doppler findings are observed, the greater the risk of preeclampsia. Normalization of UtA Doppler after 25 weeks reduces the risk of preeclampsia to 8%.

Antenatal predictors of neonatal outcome in fetal growth restriction with absent end-diastolic flow in the umbilical artery.

OBJECTIVE: Absent end-diastolic blood flow in the umbilical artery identifies growth-restricted fetuses at high risk of perinatal mortality and severe morbidity. We explored antenatal variables predictive of perinatal mortality or severe neonatal morbidity in such fetuses. STUDY DESIGN: We accessed a cohort of 39 singleton, non-malformed, growth-restricted fetuses with absent end-diastolic blood flow at less than 34 weeks between January 1995 and December 2004. The ratio of umbilical artery pulsatility index to middle cerebral artery pulsatility index was calculated to assess redistribution of the fetal arterial circulation. Prenatal and neonatal variables were compared between subjects with versus those without perinatal mortality or severe morbidity using unpaired Student t test or Fisher exact test. Statistical analysis included stepwise logistic regression and receiver operating characteristic curve analysis. P < .05 was considered significant. RESULTS: Stepwise logistic regression analysis demonstrated that the last umbilical artery/middle cerebral artery ratio (P = .02) and estimated fetal weight before delivery (P = .02) were independent predictors of adverse neonatal outcome, with an umbilical artery/middle cerebral artery ratio 1.9 or greater having a sensitivity of 75% and a 13% false-positive rate. Umbilical artery/middle cerebral artery ratio alone accounted for 54% of the variability in outcome. CONCLUSIONS: Among preterm growth-restricted fetuses with absent end-diastolic blood flow in the umbilical artery, the umbilical artery/middle cerebral artery ratio is the best predictor of neonatal mortality or severe morbidity.

Severe intrauterine growth restriction and trisomy 15 confined placental mosaicism: a case report and review of literature.

OBJECTIVES: To correlate confined placental mosaicism (CPM) for trisomy 15 with severe intrauterine growth restriction (IUGR) and early death after birth (age of 6 months). METHODS: Chromosome analysis was performed on amniotic fluid at 21st week of gestation, on peripheral blood at birth and on fibroblasts at death using conventional techniques. FISH was performed with Chromoprobe I-Multiprobe System kit and commercial probes according to manufacturer's protocol. DNA was extracted from parental and child peripheral blood, placenta tissue and skin fibroblasts, and UPD tests were done with microsatellites selected from Genome Data Base. RESULTS: The child presented severe hypospadias, micropenis, bilateral cryptorchidism and bifid scrotum, inguinal hernia, dolichomegacolon, severe thymic lymphatic depletion and heart hypertrophy, mainly involving right ventricle. Mosaic trisomy 15 (84%) was discovered by FISH on placental biopsy at term. Uniparental disomy (UPD) for chromosome 15 was excluded. Prenatal (amniotic fluid), postnatal (peripheral blood) karyotypes and analysis on skin fibroblast metaphases were normal. Since the autopsy showed some features suggesting genetic syndromes, such as CATCH22, Williams-Beuren syndrome, matUPD2, we excluded the presence of all these diseases. CONCLUSIONS: The only explanation for this clinical case seems to be the presence of tris15CPM that is reported as one of IUGR causes.

A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis.

OBJECTIVE: To compare the efficacy of S-adenosyl-l-methionine and ursodeoxycholic acid in improving serum biochemical abnormalities in gestational cholestasis. DESIGN: Randomised clinical trial. SETTING: University hospital. POPULATION: All women at <36 weeks of gestation with severe gestational cholestasis during June 1996 to December 2001. METHODS: Enrolled women were randomly assigned oral S-adenosyl-l-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg twice daily until delivery. MAIN OUTCOME MEASURES: Reduction in the concentration of serum bile acids. Other variables considered included obstetric and neonatal outcome, clinical symptoms and other laboratory measurements (serum levels of transaminases and bilirubin). The two groups were compared using Student's t test, Wilcoxon's signed rank sum test and Fisher's exact test, with a two-tailed P < 0.05 being considered significant. RESULTS: Of the 46 women enrolled, 24 received ursodeoxycholic acid and 22 S-adenosyl-l-methionine. At enrolment, gestational age, duration of therapy, rate of nulliparity, pruritus score and biochemical characteristics were similar between the groups. Both therapies significantly and equally improved pruritus. Women receiving ursodeoxycholic acid had a significantly greater improvement in the concentration of serum bile acids (P= 0.001), aspartate aminotransferase (P= 0.01), alanine aminotransferase (<0.001) and bilirubin (P= 0.002) compared with those receiving S-adenosyl-l-methionine. Duration of therapy was significantly greater in women receiving ursodeoxycholic acid compared with S-adenosyl-l-methionine (P= 0.04), whereas gestational age at delivery and rate of prematurity were similar in the two groups. CONCLUSIONS: In women with intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is more effective than S-adenosyl-l-methionine at improving the concentration of serum bile acids and other tests of liver function, whereas both therapies are equally effective at improving pruritus.

Doppler predictors of adverse neonatal outcome in the growth restricted fetus at 34 weeks' gestation or beyond.

OBJECTIVE: The study was undertaken to assess whether prenatal Doppler variables can identify cases of fetal growth restriction (FGR) approaching term who are at risk for adverse neonatal outcome. STUDY DESIGN: From a cohort of FGR cases delivered at >or=34 weeks, fetal biometry and pulsatility indices (PI) of fetal arteries obtained less than 2 weeks before delivery were related to adverse neonatal outcome, defined as admission to the neonatal intensive care unit (NICU) for indications other than low birth weight alone. RESULTS: Stepwise regression analysis showed that after controlling for gestational age at delivery and fetal biometry, only the last umbilical artery (UA) PI percentile was significantly predictive of adverse neonatal outcome (odds ratio=1.02, 95% CI 1.01-1.03, P=.02). Receiver operating characteristic curve analysis identified a UA PI at the 65th percentile as optimal predictor of adverse neonatal outcome (sensitivity=60%, false-positive rate=30%). CONCLUSION: In FGR cases delivered at >/=34 weeks' gestation, Doppler PI at the UA independently predicts the likelihood of admission to the NICU for reasons other than low birth weight alone.

Prognostic value of uterine artery Doppler velocimetry in growth-restricted fetuses delivered near term.

OBJECTIVE: We have investigated the use of uterine artery Doppler waveform analysis in growth restricted fetuses delivered at > or =34 weeks. STUDY DESIGN: Included in the study were all consecutive euploid non-malformed singleton fetuses with accurate dating diagnosed as growth restricted (sonographic abdominal circumference <10th percentile) between January 1995 and December 1998 and who were delivered at > or =34 weeks. Delivery was expedited for biophysical profile 6 or less with nonreactive nonstress test, preeclampsia, oligohydramnios, absent fetal growth over 2 weeks, absent or reversed diastolic flow in the umbilical artery (UA), or UA pulsatility index (PI) greater than the 95th percentile after 37 weeks. Neonatal outcomes were compared in cases with normal versus abnormal Doppler waveforms at the uterine arteries (defined as average resistance index >0.58 or presence of bilateral notching) using one-way analysis of variance, chi(2) test, and logistic regression analysis. A two-tailed P <.05 or an odds ratio (OR) with 95% CI not inclusive of the unity was considered significant. RESULTS: Growth-restricted fetuses with abnormal (n = 109) versus normal (n = 185) Doppler velocimetry results at the uterine arteries had similar ratios of head-to-abdominal circumference at diagnosis, but asymmetric body proportion at the last scan before delivery. Neonates of mothers with abnormal uterine artery Doppler waveforms were more frequently born of cesarean delivery, particularly for non-reassuring fetal testing (27% vs 10%, P <.001), had significantly lower gestational age at delivery (37.7 +/- 2.0 vs 38.8 +/- 1.6, P <.001), and lower birth weight percentiles (4.8 +/- 5.1 vs 9.3 +/- 10.2, P <.001). More importantly, although 5-minute Apgar scores and UA pH values were not significantly lower, they had a significantly greater risk of admission to intensive care unit for reasons other than low birth weight alone (36% vs 11%). After preeclampsia was controlled, such risk was associated with an OR of 4.1 (95% CI 2.2-7.5). CONCLUSION: In growth-restricted fetuses delivered at > or =34 weeks, presence of abnormal Doppler waveforms at the uterine arteries at diagnosis is associated with a 4-fold increased risk of adverse neonatal outcome.