Any reduction in maternal kidney mass makes a difference during pregnancy in gestational and fetal outcome.

Little is known about the effect tubulointerstitial nephropathies have in modulating maternal-fetal outcomes in pregnancy. Therefore, we analyzed the main outcomes of pregnancy in these women to gain a better understanding of the role of a reduction in maternal kidney mass. From the Torino Cagliari Observational Study (TOCOS) cohort, we selected 529 patients with a diagnosis of tubulointerstitial disease and focused on 421 patients with chronic kidney disease (CKD) stage 1, without hypertension but with proteinuria less than 0.5 g/day at referral. From a cohort of 2969 singleton deliveries from low-risk pregnancies followed in the same settings we selected a propensity score matched control cohort of 842 pregnancies match 2:1 for age, parity, body mass index, ethnicity, and origin. Time to delivery was significantly shorter in the study cohort 38.0 (Quartile 1-Quartile 3: 37.0-39.0) versus 39.0 (Q1-Q3 38.0-40.0) weeks, with respect to controls. Incidence of delivery of less than 37 gestational weeks significantly increased from controls (7.4%) to women with previous acute pyelonephritis (10.8%), other tubulointerstitial diseases (9.7%) and was the highest in patients with a single kidney (31.1%). Similarly, neonatal birthweight significantly and progressively decreased from controls (3260 g [Q1-Q3: 2980-3530]), previous acute pyelonephritis (3090 g [Q1-Q3: 2868-3405], other tubulointerstitial diseases (3110 g [Q1-Q3: 2840-3417]), and to solitary kidney (2910 g [Q1-Q3: 2480-3240]). Risk of developing preeclampsia was significantly higher in the CKD cohort (3.6% vs 1.7% in low-risk controls). Thus, even a small reduction in functional kidney mass, such as a pyelonephritic scar, is associated with a shorter duration of pregnancy and an increased risk of preterm delivery. The risk is proportional to the extent of parenchymal reduction and is highest in cases with a solitary kidney.

Reassuring pregnancy outcomes in women with mild COL4A3-5-related disease (Alport syndrome) and genetic type of disease can aid personalized counseling.

Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week. Outcomes were stratified per inheritance pattern (X-Linked AS (XLAS)), Autosomal Dominant AS (ADAS), or Autosomal Recessive AS (ARAS)). The influence of pregnancy on estimated glomerular filtration rate (eGFR)-slope was assessed in 192 pregnancies encompassing 116 women (121 with XLAS, 47 with ADAS, and 12 with ARAS). Median eGFR pre-pregnancy was over 90ml/min/1.73m2. Neonatal outcomes were favorable: 100% live births, median gestational age 39.0 weeks and mean birth weight 3135 grams. Gestational hypertension occurred during 23% of pregnancies (reference: 'general' CKD G1-G2 pregnancies incidence is 4-20%) and preeclampsia in 20%. The mean eGFR declined after pregnancy but remained within normal range (over 90ml/min/1.73m2). Pregnancy did not significantly affect eGFR-slope (pre-pregnancy ß=-1.030, post-pregnancy ß=-1.349). ARAS-pregnancies demonstrated less favorable outcomes (early preterm birth incidence 3/11 (27%)). ARAS was a significant independent predictor for lower birth weight and shorter duration of pregnancy, next to the classic predictors (pre-pregnancy kidney function, proteinuria, and chronic hypertension) though missing proteinuria values and the small ARAS-sample hindered analysis. This is the largest study to date on AS and pregnancy with reassuring results for mild AS, though inheritance patterns could be considered in counseling next to classic risk factors. Thus, our findings support personalized reproductive care and highlight the importance of investigating kidney disease-specific pregnancy outcomes.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

Adding creatinine to routine pregnancy tests: a decision tree for calculating the cost of identifying patients with CKD in pregnancy.

BACKGROUND: Even in its early stages, chronic kidney disease (CKD) is associated with adverse pregnancy outcomes. The current guidelines for pregnancy management suggest identifying risk factors for adverse outcomes but do not mention kidney diseases. Since CKD is often asymptomatic, pregnancy offers a valuable opportunity for diagnosis. The present analysis attempts to quantify the cost of adding serum creatinine to prenatal screening and monitoring tests. METHODS: The decision tree we built takes several screening scenarios (before, during and after pregnancy) into consideration, following the hypothesis that while 1:750 pregnant women are affected by stage 4-5 CKD and 1:375 by stage 3B, only 50% of CKD cases are known. Prevalence of abortions/miscarriages was calculated at 30%; compliance with tests was hypothesized at 50% pre- and post-pregnancy and 90% during pregnancy (30% for miscarriages); the cost of serum creatinine (production cost) was set at 0.20 euros. A downloadable calculator, which makes it possible to adapt these figures to other settings, is available. RESULTS: The cost per detected CKD case ranged from 111 euros (one test during pregnancy, diagnostic yield 64.8%) to 281.90 euros (one test per trimester, plus one post-pregnancy or miscarriage, diagnostic yield 87.7%). The best policy is identified as one test pre-, one during and one post-pregnancy (191.80 euros, diagnostic yield 89.4%). CONCLUSIONS: This study suggests the feasibility of early CKD diagnosis in pregnancy by adding serum creatinine to routinely performed prenatal tests and offers cost estimates for further discussion.

Pre-eclampsia is a valuable opportunity to diagnose chronic kidney disease: a multicentre study.

BACKGROUND: Pre-eclampsia (PE) and chronic kidney disease (CKD) are known to be associated. Our objective was to assess the prevalence of CKD in a large multicentre cohort of women without acknowledged CKD who experienced a PE episode. METHODS: The setting for the study was France (Le Mans, Central France) and Italy (Cagliari, Sardinia). The study participants were patients who experienced PE in 2018-19, identified from the obstetric charts. Patients with known-acknowledged CKD were excluded. Only singletons were considered. Persistent (micro)albuminuria was defined as present and confirmed at least 3 months after delivery. CKD was defined according to the Kidney Disease Outcomes Quality Initiative guidelines; urinary alterations or low eGFR confirmed at a distance of at least 3 months, or morphologic changes. Patients were divided into four groups: evidence of CKD; no evidence of CKD; unclear diagnosis-ongoing work-up; or persistent microalbuminuria. The outcome 'diagnosis of CKD' was analysed by simple and multiple logistic regressions. Temporal series (week of delivery) were analysed with Kaplan-Meier curves and Cox analysis. RESULTS: Two hundred and eighty-two PE pregnancies were analysed (Le Mans: 162; Cagliari: 120). The incidence of CKD diagnosis was identical (Le Mans: 19.1%; Cagliari: 19.2%); no significant difference was found in unclear-ongoing diagnosis (6.2%; 5.8%) and microalbuminuria (10.5%; 5.8%). Glomerulonephritis and diabetic nephropathy were more frequent in Cagliari (higher age and diabetes prevalence), and interstitial diseases in Le Mans. In the multivariate logistic regression, CKD diagnosis was associated with preterm delivery (adjusted P = 0.035). Gestation was 1 week shorter in patients diagnosed with CKD (Kaplan-Meier P = 0.007). In Cox analysis, CKD remained associated with shorter gestation after adjustment for age and parity. CONCLUSIONS: The prevalence of newly diagnosed CKD is high after PE (19% versus expected 3% in women of childbearing age), supporting a systematic nephrology work-up after PE.

Short-term morbidity and types of intrapartum hypoxia in the newborn with metabolic acidaemia: a retrospective cohort study.

OBJECTIVES: To assess labour characteristics in relation to the occurrence of Composite Adverse neonatal Outcome (CAO) within a cohort of fetuses with metabolic acidaemia. DESIGN: Retrospective cohort study. SETTING: Three Italian tertiary maternity units. POPULATION: 431 neonates born with acidaemia ≥36 weeks. METHODS: Intrapartum CTG traces were assigned to one of these four types of labour hypoxia: acute, subacute, gradually evolving and chronic hypoxia. The presence of CAO was defined by the occurrence of at least one of the following: Sarnat Score grade ≥2, seizures, hypothermia and death <7 days from birth. MAIN OUTCOME MEASURES: To compare the type of hypoxia on the intrapartum CTG traces among the acidaemic neonates with and without CAO. RESULTS: The occurrence of a CAO was recorded in 15.1% of neonates. At logistic regression analysis, the duration of the hypoxia was the only parameter associated with CAO in the case of an acute or subacute pattern (odds ratio [OR] 1.3; 95% CI 1.02-1.6 and OR 1.04; 95% CI 1.0-1.1, respectively), whereas both the duration of the hypoxic insult and the time from PROM to delivery were associated with CAO in those with a gradually evolving pattern (OR 1.13; 95% CI 1.01-1.3 and OR 1.04; 95% CI 1.0-1.7, respectively). The incidence of CAO was higher in fetuses with chronic antepartum hypoxia than in those showing CTG features of intrapartum hypoxia (64.7 vs. 13.0%; P < 0.001). CONCLUSIONS: The frequency of CAO seems related to the duration and the type of the hypoxic injury, being higher in fetuses showing CTG features of antepartum chronic hypoxia. TWEETABLE ABSTRACT: This study demonstrates that in a large population of neonates with metabolic acidaemia at birth, the overall incidence of short-term adverse outcome is around 15%. Such risk seems closely correlated to the duration and the type of hypoxic injury, being higher in fetuses admitted in labour with antepartum chronic hypoxia than those experiencing intrapartum hypoxia.

What a paediatric nephrologist should know about preeclampsia and why it matters.

Preeclampsia is a protean syndrome causing a kidney disease characterised by hypertension and proteinuria, usually considered transitory and reversible after delivery. Its prevalence ranges from 3-5 to 10% if all the related disorders are considered. This narrative review, on behalf of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology, focuses on three reasons why preeclampsia should concern paediatric nephrologists and how they can play an important role in its prevention, as well as in the prevention of future kidney and cardiovascular diseases. Firstly, all diseases of the kidney and urinary tract diagnosed in paediatric age are associated with a higher risk of adverse pregnancy-related outcomes, including preeclampsia. Secondly, babies with low birth weights (small for gestational age, born preterm, or both) have an increased risk of developing the full panoply of metabolic diseases (obesity, hypertension, early-onset cardiopathy and chronic kidney disease) and girls are at higher risk of developing preeclampsia when pregnant. The risk may be particularly high in cases of maternal preeclampsia, highlighting a familial aggregation of this condition. Thirdly, pregnant teenagers have a higher risk of developing preeclampsia and the hypertensive disorders of pregnancy, and should be followed up as high risk pregnancies. In summary, preeclampsia has come to be seen as a window on the future health of both mother and baby. Identification of subjects at risk, early counselling and careful follow-up can contribute to reducing the high morbidity linked with this disorder.

Maternal Origins of Neonatal Infections: What Do Obstetrician-Gynecologist Should/Could Do?

Neonatal infections are responsible for 20% of neonatal deaths yearly. In this review, we focused on the origins of the commoner neonatal infections, and we define the role of obstetricians. Regarding group B Streptococcus, a key measure for the prevention of neonatal infection is the vaginal-rectal culture screening at term pregnancy. Intravenous penicillin is the first-line prophylaxis at the start of labor, with intravenous ampicillin as an alternative. First-generation cephalosporins or clindamycin are recommended in case of penicillin allergy. Concerning urinary tract infections (UTIs), guidelines recommend complete urinalysis and urine culture in the first trimester of pregnancy for the screening of asymptomatic bacteriuria. For lower UTIs, guidelines recommend nitrofurantoin as first-choice antibiotic. Amoxicillin or cefalexin are second-line antibiotics. For upper UTIs, guidelines recommend cephalexin per os as first line. Candida spp. colonization affects 20% of pregnant women; however, congenital fetal candidosis and Candida amnionitis are rare. First-line treatment in case of symptomatic vaginitis during pregnancy or asymptomatic colonization during the third trimester is vaginal clotrimazole. Fluconazole is not approved in pregnancy, especially during the first trimester. Genital mycoplasmas colonization during pregnancy is usually asymptomatic and associated with bacterial vaginosis. Colonization is related to neonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), pneumonia, chorioamnionitis, and sepsis. Macrolides are the first-line treatment along with lactobacillus supplementation. In cases of preterm premature rupture of membranes or preterm labor, ceftriaxone, clarithromycin, and metronidazole are required to prevent intra-amniotic infection. Intra-amniotic infection affects 1 to 5% of deliveries at term and one-third of preterm ones and is associated with perinatal death, early-onset neonatal sepsis, RDS, BPD, pneumonia, meningitis, and prematurity-related diseases. Guidelines recommend a combination of ampicillin and gentamicin, and in case of caesarean section, an additional dose of clindamycin or metronidazole is required. In conclusion, obstetricians should be aware that the treatment of maternal infection during pregnancy can prevent potentially lethal infections in the newborn. KEY POINTS: · Part of neonatal infections starts from maternal infections that must be treated during pregnancy.. · Streptococcus group B and asymptomatic bacteriuria should be investigated in pregnancy and treated.. · Mycoplasma and ureaplasma vaginal colonization during pregnancy is related to negative neonatal outcomes..

Intrapartum sonographic assessment of the fetal head flexion in protracted active phase of labor and association with labor outcome: a multicenter, prospective study.

BACKGROUND: To date, no research has focused on the sonographic quantification of the degree of flexion of the fetal head in relation to the labor outcome in women with protracted active phase of labor. OBJECTIVE: This study aimed to assess the relationship between the transabdominal sonographic indices of fetal head flexion and the mode of delivery in women with protracted active phase of labor. STUDY DESIGN: Prospective evaluation of women with protracted active phase of labor recruited across 3 tertiary maternity units. Eligible cases were submitted to transabdominal ultrasound for the evaluation of the fetal head position and flexion, which was measured by means of the occiput-spine angle in fetuses in nonocciput posterior position and by means of the chin-to-chest angle in fetuses in occiput posterior position. The occiput-spine angle and the chin-to-chest angle were compared between women who had vaginal delivery and those who had cesarean delivery. Cases where obstetrical intervention was performed solely based on suspected fetal distress were excluded. RESULTS: A total of 129 women were included, of whom 43 (33.3%) had occiput posterior position. Spontaneous vaginal delivery, instrumental delivery, and cesarean delivery were recorded in 66 (51.2%), 17 (13.1%), and 46 (35.7%) cases, respectively. A wider occiput-spine angle was measured in women who had vaginal delivery compared with those submitted to cesarean delivery owing to labor dystocia (126±14 vs 115±24; P<.01). At the receiver operating characteristic curve, the area under the curve was 0.675 (95% confidence interval, 0.538-0.812; P<.01), and the optimal occiput-spine angle cutoff value discriminating between cases of vaginal delivery and those delivered by cesarean delivery was 109°. A narrower chin-to-chest angle was measured in cases who had vaginal delivery compared with those undergoing cesarean delivery (27±33 vs 56±28 degrees; P<.01). The area under the curve of the chin-to-chest angle in relation to the mode of delivery was 0.758 (95% confidence interval, 0.612-0.904; P<.01), and the optimal cutoff value discriminating between vaginal delivery and cesarean delivery was 33.0°. CONCLUSION: In women with protracted active phase of labor, the sonographic demonstration of fetal head deflexion in occiput posterior and in nonocciput posterior fetuses is associated with an increased incidence of cesarean delivery owing to labor dystocia. Such findings suggest that intrapartum ultrasound may contribute in the categorization of the etiology of labor dystocia.

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia.

Preeclampsia is a pregnancy-related syndrome of variable severity, classically characterized by acute kidney involvement, with hypertension and/or proteinuria and reduced kidney function. Once considered a self-limited disease healed by delivery, it is now acknowledged that preeclampsia can affect cardiovascular and kidney health in the long term. The entity of risk has not been established and consequently follow-up policies have not been defined. Here we undertook a systematic review to gain better insights into the need for post-preeclampsia follow-up. Articles published between January 2000 and March 2018 were selected, dealing with at least 20 preeclampsia patients, with follow-up of 4 years or more (MEDLINE, Embase, and Cochrane Library). No quality selection or language restriction was performed. Of the 10,510 titles and abstracts originally considered, 21 papers were selected, providing information on 110,803 cases with and 2,680,929 controls without preeclampsia, with partial overlap between studies on the same databases. Heterogeneity was high, and a random meta-analytic model selected. The increase in risk of end stage renal disease after preeclampsia was significant (meta-analytic risk ratios (95% confidence interval) 6.35 (2.73-14.79)); the risk of albuminuria and chronic kidney disease increased but statistical significance was not reached (4.31 (0.95-19.58) and 2.03 (0.58-7.32), respectively). Translating meta-analytic risk into the number of patients who need follow-up to detect one adverse event, 310 patients with preeclampsia are needed to identify one woman with end stage renal disease or four to identify one woman with albuminuria. Heterogeneity in definitions, insufficient follow-up and incomplete recruitment may account for discrepancies. Thus, preeclampsia significantly increases the risk of end stage renal disease. However, there is lack of sufficient data to show a relationship between preeclampsia, albuminuria and chronic kidney disease, underlining the need for further prospective studies.

Prediction of spontaneous vaginal delivery in nulliparous women with a prolonged second stage of labor: the value of intrapartum ultrasound.

BACKGROUND: A limited number of studies have addressed the role of intrapartum ultrasound in the prediction of the mode of delivery in women with prolonged second stage of labor. OBJECTIVE: The objective of the study was to evaluate the role of transabdominal and transperineal sonographic findings in the prediction of spontaneous vaginal delivery among nulliparous women with prolonged second stage of labor. STUDY DESIGN: This was a 2-center prospective study conducted at 2 tertiary maternity units. Nulliparous women with a prolonged active second stage of labor, as defined by active pushing lasting more than 120 minutes, were eligible for inclusion. Transabdominal ultrasound to evaluate the fetal head position and transperineal ultrasound for the measurement of the midline angle, the head-perineum distance, and the head-symphysis distance were performed in between uterine contractions and maternal pushes. At transperineal ultrasound the angle of progression was measured at rest and at the peak of maternal pushing effort. The delta angle of progression was defined as the difference between the angle of progression measured during active pushing at the peak of maternal effort and the angle of progression at rest. The sonographic findings of women who had spontaneous vaginal delivery vs those who required obstetric intervention, either vacuum extraction or cesarean delivery, were evaluated and compared. RESULTS: Overall, 109 were women included. Spontaneous vaginal delivery and obstetric intervention were recorded in 40 (36.7%) and 69 (63.3%) patients, respectively. Spontaneous vaginal delivery was associated with a higher rate of occiput anterior position (90% vs 53.2%, P < .0001), lower head-perineum distance and head-symphysis distance (33.2 ± 7.8 mm vs 40.1 ± 9.5 mm, P = .001, and 13.1 ± 4.6 mm vs 19.5 ± 8.4 mm, P < .001, respectively), narrower midline angle (29.6° ± 15.3° vs 54.2° ± 23.6°, P < .001) and wider angle of progression at the acme of the pushing effort (153.3° ± 19.8° vs 141.8° ± 25.7°, P = .02) and delta-angle of progression (17.3° ± 12.9° vs 12.5° ± 11.0°, P = .04). At logistic regression analysis, only the midline angle and the head-symphysis distance proved to be independent predictors of spontaneous vaginal delivery. More specifically, the area under the curve for the prediction of spontaneous vaginal delivery was 0.80, 95% confidence interval (0.69-0.92), P < .001, and 0.74, 95% confidence interval (0.65-0.83), P = .002, for the midline angle and for the head-symphysis distance, respectively. CONCLUSION: Transabdominal and transperineal intrapartum ultrasound parameters can predict the likelihood of spontaneous vaginal delivery in nulliparous women with prolonged second stage of labor.

Risk of adverse pregnancy outcomes by pre-pregnancy Body Mass Index among Italian population: a retrospective population-based cohort study on 27,807 deliveries.

PURPOSE: To estimate the impact of increasing pre-pregnancy Body Mass Index (BMI) on the risk of adverse maternal and perinatal outcomes, in patients who delivered in an Italian tertiary care Obstetric department. METHODS: Data, related to women who delivered at Sant'Anna Hospital, Turin, between 2011 and 2015, were collected retrospectively from the hospital database. According to BMI, women were considered as normal weight, overweight, and class 1, 2 and 3 obese (WHO criteria). Logistic regression analysis studied the impact of BMI on maternal and neonatal outcomes, adjusting results for maternal age and parity. Adjusted absolute risks of each outcome were reported according to incremental values in pre-pregnancy BMI. RESULTS: A total of 27,807 women were included. 75.8% of pregnancies occurred among normal-weight women, whereas 16.7% were overweight, and 7.5% obese women (5.4% class 1, 1.7% class 2 and 0.4% class 3). A 10% decrease in pre-pregnancy BMI was associated with a reduction of at least 15% of Gestational diabetes mellitus (GDM), preeclampsia, maternal admission to intensive care unit (ICU), macrosomia, APGAR 5' < 6 and neonatal admission to ICU. GDM and preeclampsia resulted in the highest reduction being almost 30%. Larger differences in BMI (20-25%) corresponded to at least a 10% in reduction of risk of preterm and very preterm delivery and emergency cesarean section. Differences in maternal pre-pregnancy BMI had no impact on the frequency of shoulder dystocia and stillbirth. CONCLUSIONS: This study offers a quantitative estimation of negative impact of pre-pregnancy obesity on the most common pregnancy and perinatal complications.

Maternal-foetal outcomes in pregnant women with glomerulonephritides. Are all glomerulonephritides alike in pregnancy?

In spite of the interest for chronic renal diseases (CKD) in pregnancy data on specific diseases is fragmentary; while recent studies analysed the most common glomerulonephritides (GN), none was addressed at GN as a group. The aim of our study was to analyse the main pregnancy-related outcomes in GN patients in a large multicentre cohort. Patients with a diagnosis of GN were selected from the TOCOS cohort (TOCOS: TOrino Cagliari Observational Study): out of 714 singleton deliveries GN was the diagnosis in 126; lupus GN and IgA nephropathy accounted for 37 and 33 cases; 1418 low-risk singleton deliveries followed-up in the same Centers served as controls (non diabetic, non nephropathic, non obese women, without any other known chronic illness; pregnancies after ovodonation or in vitro fertilisation were excluded, if declared). Multiple regression analysis considered: pre-term (<37 weeks), early preterm delivery (<34 weeks), small for gestational age baby (SGA) and the development of hypertension, proteinuria and preeclampsia (PE) limiting this outcome to the cases without hypertension and proteinuria at baseline. The population consisted mainly of early CKD stages (stage 1: 61.9%; hypertension 27.8%; proteinuria <0.5 g/day: 55.7%). Age and parity were not different in cases and low-risk controls (age: 31.20 ± 5.5 vs 31.24 ± 5.5 years, primiparous 56.3% vs 57.5%). The incidence of preterm and early preterm delivery was higher in GN versus controls and increased commensurately with CKD stage. In the multivariate analysis, CKD stage was significantly associated with early preterm delivery and development-doubling of proteinuria (odds ratio (OR) around 3 in both), while the OR for baseline hypertension did not reach statistical significance. While the risk pattern did not differ in lupus and non-lupus GN, a significantly higher OR of PE was observed in IgA nephropathy (OR 28.09 versus other GN); risk for pre-term delivery was not increased (OR 0.27 (0.06-1.11)), thereby suggesting "late-maternal" PE. In conclusion, within the limits of heterogeneity and small numbers, our analysis identifies proteinuria as the most reliable risk marker for adverse pregnancy outcomes and suggests a specific association between IgA nephropathy and late-maternal PE.

Evidence of lower oxygen reserves during labour in the growth restricted human foetus: a retrospective study.

BACKGROUND: The aim of the present study is to test the hypothesis that Growth Restricted foetuses (FGR) have the tendency to develop more pathological cardiotocograpic tracings during labour than do appropriate for gestational age foetuses and that there is a shorter time lapse from the beginning of labour and the advent of a pathological cardiotocograpic tracing. METHODS: The study was carried out at the Maternal-Foetal Medicine Unit of the Sant'Anna University Hospital, Turin, Italy. A total of 930 foetuses born at term between January and December 2012 were analysed: 355 small for gestational age (SGA) comprising both constitutional small for gestational age and growth restricted foetuses (cases group) and 575 Appropriate for Gestational Age (AGA) foetuses (control group). Tracings were evaluated independently by two obstetric consultants, according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. The main outcomes considered were the incidence of pathological cardiotocograpic tracings and the time interval between the beginning of labour and the advent of pathological cardiotocograpic tracing. The Student's t-test, chi-square test and ANOVA were used for comparisons between cases and controls and amongst groups. Significance was set at <0.05. Univariate and multivariate odds-ratios were calculated. RESULTS: Foetuses with birthweight <3rd centile (growth restricted foetuses) more frequently presented pathological cardiotocograpic tracings in labour than did controls (43.8% vs. 21.6%; p < 0.001). Pathological cardiotocograpic tracing developed faster in the foetuses with birthweight <3rd centile group (53', 0'-277') than it did in the control group (170.5', 0'-550'; p < 0.05). A higher induction rate was observed in the cases (29.6%) than in the control group (17%), with statistical significance p < 0.001. To correct for this possible confounding factor a multivariate logistic regression analysis was performed. It confirmed a statistically significant increased risk of pathological cardiotocographic tracings in the FGR group (OR 1.63; CI 1.30-2.05). CONCLUSION: The results confirm the hypothesis that Growth Restricted foetuses (FGR) have fewer oxygen reserves to deal with labour. Our results underscore the importance of the prenatal detection of these foetuses and of their continuous cardiotocographic monitoring during labour.

Pregnancy in dialysis patients in the new millennium: a systematic review and meta-regression analysis correlating dialysis schedules and pregnancy outcomes.

BACKGROUND: Advances have been made in the management of pregnancies in women receiving dialysis; however, single-centre studies and small numbers of cases have so far precluded a clear definition of the relationship between dialysis schedules and pregnancy outcomes. The aim of the present systematic review was to analyse the relationship between dialysis schedule and pregnancy outcomes in pregnancies in chronic dialysis in the new millennium. METHODS: Medline-PubMed, Embase and the Cochrane library were searched (1 January 2000-31 December 2014: MESH, Emtree, free terms on pregnancy and dialysis). A separate analysis was performed for case series (more than five cases) and case reports. Meta-regression was performed in case series dealing with the larger subset of haemodialysis (HD) patients; case reports were analysed separately [according to peritoneal dialysis (PD) versus HD; conception before or during dialysis]. RESULTS: We obtained 190 full texts and 25 congress abstracts from 2048 references. We selected 101 full papers and 25 abstracts (36 series; 90 case reports), for a total of 681 pregnancies in 647 patients. In the case series (574 pregnancies in 543 patients), preterm delivery was extremely frequent (83%). Meta-regression analysis showed a relationship between hours of dialysis per week in HD and preterm delivery, and was significant for preterm deliveries (<37 gestational weeks: P = 0.044; r2 = 0.22) and for small for gestational age (SGA) (P = 0.017; r2 = 0.54). SGA was closely associated with the number of dialysis sessions per week (P = 0.003; r2 = 0.84). Case report analysis suggests a lower incidence of SGA on HD versus PD (31 versus 66.7%; P = 0.015). No evidence of an increased risk of congenital abnormality was found in the retrieved papers. CONCLUSIONS: Data on pregnancy on dialysis are heterogeneous but rapidly accumulating; the main determinant of outcomes on HD is the dialysis schedule. The differences between PD and HD should be further analysed.

Pregnancy outcomes after kidney graft in Italy: are the changes over time the result of different therapies or of different policies? A nationwide survey (1978-2013).

BACKGROUND: Kidney transplantation is the treatment of choice to restore fertility to women on renal replacement therapy. Over time, immunosuppressive, support therapies and approaches towards high-risk pregnancies have changed. The aim of this study was to analyse maternal-foetal outcomes in two cohorts of transplanted women who delivered a live-born baby in Italy in 1978-2013, dichotomized into delivery before and after January 2000. METHODS: A survey involving all the Italian transplant centres was carried out, gathering data on all pregnancies recorded since the start of activity at each centre; the estimated nationwide coverage was 75%. Data on cause of ESRD, dialysis, living/cadaveric transplantation, drug therapy, comorbidity, and the main maternal-foetal outcomes were recorded and reviewed. Data were compared with a low-risk cohort of pregnancies from two large Italian centres (2000-14; Torino and Cagliari Observational Study cohort). RESULTS: The database consists of 222 pregnancies with live-born babies after transplantation (83 before 2000 and 139 in 2000-13; 68 and 121 with baseline and birth data, respectively), and 1418 low-risk controls. The age of the patients significantly increased over time (1978-99: age 30.7 ± 3.7 versus 34.1 ± 3.7 in 2000-13; P < 0.001). Azathioprine, steroids and cyclosporine A were the main drugs employed in the first time period, while tacrolimus emerged in the second. The prevalence of early preterm babies increased from 13.4% in the first to 27.1% in the second period (P = 0.049), while late-preterm babies non-significantly decreased (38.8 versus 33.1%), thus leaving the prevalence of all preterm babies almost unchanged (52.2 and 60.2%; P = 0.372). Babies below the 5th percentile decreased over time (22.2 versus 9.6%; P = 0.036). In spite of high prematurity rates, no neonatal deaths occurred after 2000. The results in kidney transplant patients are significantly different from controls both considering all cases [preterm delivery: 57.3 versus 6.3%; early preterm: 22.2 versus 0.9%; small for gestational age (SGA): 14 versus 4.5%; P < 0.001] and considering only transplant patients with normal kidney function [preterm delivery: 35 versus 6.3%; early preterm: 10 versus 0.9%; SGA: 23.7 versus 4.5% (P < 0.001); risks increase across CKD stages]. Kidney function remained stable in most of the patients up to 6 months after delivery. Multiple regression analysis performed on the transplant cohort highlights a higher risk of preterm delivery in later CKD stages, an increase in preterm delivery and a decrease in SGA across periods. CONCLUSIONS: Pregnancy after transplantation has a higher risk of adverse outcomes compared with the general population. Over time, the incidence of SGA babies decreased while the incidence of 'early preterm' babies increased. Although acknowledging the differences in therapy (cyclosporine versus tacrolimus) and in maternal age (significantly increased), the decrease in SGA and the increase in prematurity may be explained by an obstetric policy favouring earlier delivery against the risk of foetal growth restriction.

Hypertension in CKD Pregnancy: a Question of Cause and Effect (Cause or Effect? This Is the Question).

Chronic kidney disease (CKD) is increasingly encountered in pregnancy, and hypertension is frequently concomitant. In pregnancy, the prevalence of CKD is estimated to be about 3%, while the prevalence of chronic hypertension is about 5-8%. The prevalence of hypertension and CKD in pregnancy is unknown. Both are independently related to adverse pregnancy outcomes, and the clinical picture merges with pregnancy-induced hypertension and preeclampsia. Precise risk quantification is not available, but risks linked to CKD stage, hypertension, and proteinuria are probably multiplicative, each at least doubling the rates of preterm and early preterm delivery, small for gestational age babies, and related outcomes. Differential diagnosis (based upon utero-placental flows, fetal growth, and supported by serum biomarkers) is important for clinical management. In the absence of guidelines for hypertension in CKD pregnancies, the ideal blood pressure goal has not been established; we support a tailored approach, depending on compliance, baseline control, and CKD stages, with strict blood pressure monitoring. The choice of antihypertensive drugs and the use of diuretics and of erythropoiesis-stimulating agents (ESAs) are still open questions which only future studies may clarify.

Vegan-vegetarian low-protein supplemented diets in pregnant CKD patients: fifteen years of experience.

BACKGROUND: Pregnancy in women with advanced CKD becoming increasingly common. However, experience with low-protein diets in CKD patients in pregnancy is still limited. Aim of this study is to review the results obtained over the last 15 years with moderately restricted low-protein diets in pregnant CKD women (combining: CKD stages 3-5, proteinuria: nephrotic at any time, or > =1 g/24 at start or referral; nephrotic in previous pregnancy). CKD patients on unrestricted diets were employed for comparison. STUDY PERIOD: January, 2000 to September, 2015: 36 on-diet pregnancies (31 singleton deliveries, 3 twin deliveries, 1 pregnancy termination, 1 miscarriage); 47 controls (42 singleton deliveries, 5 miscarriages). The diet is basically vegan; since occasional milk and yoghurt are allowed, we defined it vegan-vegetarian; protein intake (0.6-0.8 g/Kg/day), keto-acid supplementation, protein-unrestricted meals (1-3/week) are prescribed according to CKD stage and nutritional status. Statistical analysis was performed as implemented on SPSS. RESULTS: Patients and controls were similar (p: ns) at baseline with regard to age (33 vs 33.5), referral week (7 vs 9), kidney function (CKD 3-5: 48.4 % vs 64.3 %); prevalence of hypertension (51.6 % vs 40.5 %) and proteinuria >3 g/24 h (16.1 % vs 12.2 %). There were more diabetic nephropathies in on-diet patients (on diet: 31.0 % vs controls 5.3 %; p 0.007 (Fisher)) while lupus nephropathies were non-significantly higher in controls (on diet: 10.3 % vs controls 23.7 %; p 0.28 (Fisher)). The incidence of preterm delivery was similar (<37 weeks: on-diet singletons 77.4 %; controls: 71.4 %). The incidence of other adverse pregnancy related outcomes was non-significantly lower in on-diet patients (early preterm delivery: on diet: 32.3 % vs controls 35.7 %; birth-weight = <1.500 g: on diet: 9.7 % vs controls 23.8 %). None of the singletons in the on-diet series died, while two perinatal deaths occurred among the controls (p = 0.505). The incidence of small for gestational age (SGA <10th centile) and/or extremely preterm babies (<28th week) was significantly lower in singletons from on-diet mothers than in controls (on diet: 12.9 % vs controls: 33.3 %; p: 0.04 (Fisher)). CONCLUSION: Moderate protein restriction in the context of a vegan-vegetarian supplemented diet is confirmed as a safe option in the management of pregnant CKD patients.

Risk of Adverse Pregnancy Outcomes in Women with CKD.

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; "general" combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1% versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a "baseline risk" for adverse pregnancy-related outcomes linked to CKD.

Children of a lesser god or miracles? An emotional and behavioural profile of children born to mothers on dialysis in Italy: a multicentre nationwide study 2000-12.

BACKGROUND: Pregnancy on dialysis is increasingly being reported. This study evaluates the behavioural profile of the children of mothers on dialysis and the parental stress their mothers undergo when compared with a group of mothers affected by a different chronic disease (microcythaemia) and a group of healthy control mothers. METHODS: Between 2000 and 2012, 23 on-dialysis mothers gave birth to 24 live-born children in Italy (23 pregnancies, 1 twin pregnancy, one of the twins deceased soon after delivery); of these, 16 mothers and 1 father (whose wife died before the inquiry) were included in the study (1 mother had died and the father was unavailable; 2 were not asked to participate because their children had died and 3 were unavailable; children: median age: 8.5, min-max: 2-13 years). Twenty-three mothers affected by transfusion-dependent microcythaemia or drepanocitosis (31 pregnancies, 32 children) and 35 healthy mothers (35 pregnancies, 35 children; median age of the children: 7, min-max: 1-13 years) were recruited as controls. All filled in the validated questionnaires: 'Child Behaviour Checklist' (CBCL) and the 'Parental Stress Index-Short Form' (PSI-SF). RESULTS: The results of the CBCL questionnaire were similar for mothers on dialysis and healthy controls except for pervasive developmental problems, which were significantly higher in the dialysis group, while microcythaemia mothers reported higher emotional and behavioural problems in their children in 8 CBCL sub-scales. Two/16 children in the dialysis and 3/32 in the microcythaemia group had pathological profiles, as assessed by T-scores (p: ns). PSI-SF indicated a normal degree of parental stress in microcythaemia subjects and healthy controls, while mothers on dialysis declared significantly lower stress, suggesting a defensive response in order to minimize problems, stress or negativity in their relationship with their child. CONCLUSIONS: According to the present analysis, the emotional and behavioural outcome is normal in most of the children from on-dialysis mothers. A 'positive defence' in the dialysis mothers should be kept in mind when tailoring psychological support for this medical miracle.