Maternal Circulating Vitamin D Level, Targeted Supplementation, and Perinatal Outcomes in Twin Pregnancy.

BACKGROUND: Vitamin D deficiency is associated with several obstetric complications in singleton pregnancy. The aim of this study was to assess whether vitamin D levels affect the outcomes of twin pregnancy and if targeted supplementation can improve perinatal outcomes. METHODS: The serum vitamin D levels of 143 women with twin pregnancies were measured during their first trimester. Those with insufficient (10-30 ng/mL; IL group) or severely deficient (<10 ng/mL, DL group) vitamin D levels were supplemented. In the third trimester, vitamin D levels were reassessed. Perinatal outcomes of the IL and DL groups were compared with those of patients with sufficient levels (>30 ng/mL, SL group) since the beginning of pregnancy. RESULTS: Women in the IL and DL groups had a higher incidence of hypertensive disorders of pregnancy (HDP) compared to the SL group (24.8% and 27.8% vs. 12.5%, p = 0.045): OR = 1.58 for the IL group and 1.94 for the DL group compared to the SL group. In patients whose vitamin D levels were restored after supplementation, HDP incidence was lower than in patients who remained in the IL or DL groups (23.4% vs. 27.3%) but higher than those who were always in the SL group (12.5%). CONCLUSIONS: Insufficient or severely deficient levels of vitamin D in the first trimester are associated with an increased risk of HDP in twin pregnancy. The beneficial effect of targeted vitamin D supplementation in reducing HDP seems limited.

Is the Early Screening of Lower Genital Tract Infections Useful in Preventing Adverse Obstetrical Outcomes in Twin Pregnancy?

Objectives: Twin pregnancy implies a higher risk of preterm birth and, consequently, higher neonatal morbidity and mortality. In singleton pregnancies, infections of the lower genital tract (LGTIs) and bacterial vaginosis are associated with preterm labor, and their early detection has been proven effective in reducing complications like the preterm premature rupture of membranes (pPROM) and preterm delivery. The same evidence, however, is lacking for twin pregnancies. This study aimed to evaluate whether the early identification and treatment of LGTIs or bacterial vaginosis in asymptomatic women with twin pregnancy could reduce the rate of miscarriages, pPROM, and preterm birth. Methods: This study performed a retrospective comparison of 285 women with a multiple pregnancy submitted for a cervico-vaginal swab only at 20-22 weeks (Single Test Group, STG), and 199 women who underwent the swab at 12-14 and again at 20-22 weeks (Double Test Group, DTG). All women included in the study had a twin pregnancy and were followed up at Sant'Anna Hospital, Turin (Italy), between September 2012 and February 2021. Results: In STG, 21.7% of patients had a positive swab; in DTG, 19.9% had an early positive swab that was immediately treated by targeted antibiotics; and 16.7% had a mid-pregnancy positive swab. The DTG showed a significantly lower incidence of pPROM in univariate analysis (14.4% vs. 23.1%, p = 0.021), which was confirmed by multivariate analysis (OR 0.55, CI 0.33-0.93, p = 0.025). Conclusions: Our study suggests that, in asymptomatic women with twin pregnancy, the early screening of LGTIs and bacterial vaginosis by a cervico-vaginal swab at 12-14 weeks of gestational age is effective in reducing the risk of pPROM.

Retrospective comparison of monochorionic diamniotic twin pregnancies stratified by spontaneous or artificial conception.

OBJECTIVES: To compare outcomes of monochorionic diamniotic (MCDA) twin pregnancies by in vitro fertilization (IVF) vs. spontaneously conceived counterparts. METHODS: Retrospective comparison. Data about MCDA twin pregnancies, conceived spontaneously or by IVF, attending the Twin Pregnancy Care Unit of Sant'Anna Hospital in Turin (Italy) between January 1st 2010 and March 31st 2022, were collected retrospectively. Obstetric, fetal, and neonatal outcomes of MCDA twin pregnancies by IVF were compared to those of spontaneously conceived counterparts. Data were described by univariate and multivariate analysis. RESULTS: 541 MCDA twin pregnancies were included in the study, among which 45 conceived by IVF and 496 spontaneously conceived. Women with IVF twins were older than those who conceived spontaneously (36.7 ± 5.7 vs. 32.1 ± 5.2 years; p<0.001). No significant difference in the prevalence of pregnancy complications between the two groups was found, except for an increased incidence of hypertensive disorders among IVF pregnancies (17.8 vs. 8.5 %; p=0.039), which resulted nonsignificant after adjusting for maternal age and parity (aOR 1.9, 95 % CI 0.8-4.6). Data about 1,046 live born babies (90 conceived by IVF and 956 spontaneously) were also collected: perinatal outcomes did not differ between the two groups. CONCLUSIONS: Our results suggest that MCDA twin pregnancies following IVF are not at increased risk of adverse outcomes compared to spontaneous MCDA twin pregnancies.

Gestational Diabetes Mellitus Does Not Worsen Obstetrical and Neonatal Outcomes of Twin Pregnancy.

The specific effects of gestational diabetes mellitus (GDM) on twin pregnancy outcomes, which are at high risk per se, are unclear. The present study analyzes outcomes of twin pregnancies complicated by GDM (n = 227) by comparing them with GDM singleton pregnancies (n = 1060) and with twin pregnancies without GDM (n = 1008), all followed up at Sant'Anna Hospital, Turin (Italy), between January 2010 and March 2020. The prevalence of GDM among twin pregnancies (n = 1235) was 18.4%. Compared to GDM singletons, GDM twins had higher rates of preeclampsia (aOR 2.0; 95% CI 1.2-3.8), cesarean section (aOR 7.5; 95% CI 5.2-10.8), and neonatal hypoglycemia (aOR 2.5; 95% CI 1.1-5.3). They had a higher incidence of abnormal 2 h OGTT values (aOR 7.1; 95% CI: 3.2-15.7) and were less likely to require insulin therapy (aOR 0.5; 95% CI: 0.3-0.7). In comparison with twin pregnancies without GDM, women with GDM twins were significantly older (35.0 vs. 33.0 years; p < 0.001) and had higher BMI (23.0 versus 22.0 kg/m2; p < 0.001); they had a higher incidence of LGA newborns (aOR 5.3; 95% CI 1.7-14.8), and lower incidence of low APGAR scores (0.5; 95% CI 0.3-0.9). Overall, GDM does not worsen outcomes of twin pregnancy, which is per se at high risk for adverse outcomes.

Arabin cervical pessary to prevent preterm birth in twin pregnancies with short cervix.

A retrospective study was conducted to evaluate the effect of Arabin cervical pessary in twin pregnancies with cervical length (CL) <25 mm between 21 and 31 weeks. Forty patients receiving pessary were matched with 40 controls without pessary. They were matched for gestational age (GA) at admission and CL. GA at delivery, delivery before 36, 34 and 32 weeks, latency between detection of short cervix and delivery, and duration of hospital admission were compared between groups. Women with the pessary delivered at higher GA compared to controls (35 vs. 33 weeks, p = 0.02). Cervical pessary significantly reduced the incidence of delivery <36 and < 34 weeks (p < 0.05), but not before 32 weeks. Interval between detection of short cervix and delivery was longer in the pessary group and duration of hospital admission was shorter (p = 0.03) compared to women without pessary.

Pre-eclampsia or chronic kidney disease? The flow hypothesis.

BACKGROUND: Chronic kidney disease (CKD) and pre-eclampsia (PE) occur in 3-5% of pregnancies. They often share hypertension and proteinuria and a differential diagnosis may be impossible. However, in PE, the pathogenesis is related to abnormal placentation, which can be detected by abnormal uterine and umbilical Doppler flow velocities, while in CKD, an intrinsic kidney disease is present. We hypothesize that Doppler studies can help to differentiate PE from CKD, as the flow velocities are altered in PE and normal in CKD. METHODS: We retrospectively selected patients who were followed in our Materno-Foetal Unit (2005-10) and had at least one flow measurement in our setting. CKD patients were included in the presence of proteinuria (≥ 300 mg/day) and hypertension, mimicking PE. The clinical charts were reviewed by the same operators; the clinical diagnoses were taken as reference. Three flow patterns were considered: alteration of both flow velocity waveforms (FVWs) (uterine and umbilical arteries), hypothesized as predictive of PE; normal FVWs at both levels, hypothesized as predictive of CKD; altered FVW in either artery, considered 'mixed'. Uterine FVWs were considered pathological according to the classical cut-point (RI > 0.58). Umbilical flows were evaluated according to standards adjusted for gestational age. Statistical analysis was performed in SPSS. RESULTS: The analysis included 61 cases. The presence of normal FVWs was significantly associated with the diagnosis of CKD (P = 0.0018). Conversely, the presence of both altered flows was significantly associated with PE (P = 0.0233). CONCLUSIONS: In the presence of proteinuria and hypertension, normal flows suggest CKD altered flows PE. Prospective studies are needed to refine this hypothesis based on the first Doppler criteria supporting the differential diagnosis between CKD and PE.

Multiple pregnancies in CKD patients: an explosive mix.

BACKGROUND AND OBJECTIVES: CKD and multiple pregnancies bear important risks for pregnancy outcomes. The aim of the study was to define the risk for adverse pregnancy-related outcomes in multiple pregnancies in CKD patients in comparison with a control group of "low-risk" multiple pregnancies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study was performed in the Maternal Hospital of the University of Turin, Italy. Of 314 pregnancies referred in CKD (2000-2011), 20 were multiple (15 twin deliveries). Control groups consisted of 379 low-risk multiple pregnancies (314 twin deliveries) and 19 (15 twin deliveries) cases with hypertension-collagen diseases. Baseline data and outcomes were compared by univariate and logistic regression analyses. RESULTS: The prevalence of multiple pregnancies was relatively high in the CKD population (6.4%); all referred cases were in early CKD stages (I-II); both creatinine (0.68 to 0.79 mg/dl; P=0.010) and proteinuria (0.81 to 3.42 g/d; P=0.041) significantly increased from referral to delivery. No significant difference in demographic data at baseline was found between cases and low-risk controls. CKD was associated with higher risk of adverse pregnancy outcomes versus low-risk twin pregnancies. Statistical significance was reached for preterm delivery (<34 weeks: 60% vs 26.4%; P=0.005; <32 weeks: 53.3% vs 12.7%; P<0.001), small for gestational age babies (28.6% vs 8.1%; P<0.001), need for Neonatal Intensive Care Unit (60% vs 12.7%; P<0.001), weight discordance between twins (40% vs 17.8%; P=0.032), and neonatal and perinatal mortality (6.6% vs 0.8%; P=0.032). CONCLUSION: This study suggests that maternal-fetal risks are increased in multiple pregnancies in the early CKD stages.

Protean presentation and multiple challenges of nephrocalcinosis in pregnancy (six pregnancies in four patients).

BACKGROUND: Nephrocalcinosis is an umbrella term covering increased content of calcium salts in the renal parenchyma, interstitial damage and potential evolution towards renal failure. Pregnancy is often the first occasion for biochemical or imaging tests in young women and may allow early diagnosis. Conversely, even mild kidney disease may represent a challenge in pregnancy. AIM: The aim of this study was to report on four patients in whom nephrocalcinosis was first diagnosed during pregnancy, exemplifying the protean presentation and multiple challenges of nephrocalcinosis in pregnancy. METHODS: This is a case series study including data on all pregnancies prospectively gathered in the Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (2000-11). RESULTS: Six pregnancies were observed in four patients (31-35 years; one twin pregnancy, one ongoing, one patient with three pregnancies). Symptoms were oedema in two (later developed in a further patient), renal functional impairment and electrolyte imbalance in two each. Two patients developed hypertension late in pregnancy. Electrolyte imbalance was life-threatening in one patient (severe acidosis, severe hyperkalaemia: 7.5 mEq/L). Delivery was by Caesarean section in three patients, preterm in one. Multiple or long hospitalizations for metabolic reasons were needed in three patients, the fourth was hospitalized for obstetric reasons. In all patients, diagnosis of nephrocalcinosis was made at ultrasounds during basic nephrological evaluation, confirmed at computerized tomography scan in three. The pathogenesis was linked to diuretic abuse in one case and to collagen disease, inborn errors and prematurity, possibly associated with diuretic misuse, in the others. CONCLUSION: Nephrocalcinosis may have protean presentations in pregnancy. The risk of severe electrolyte derangements, oedema and hypertension warrants strict clinical surveillance.

Pregnancy in chronic kidney disease: need for a common language.

INTRODUCTION: Chronic kidney disease (CKD) is a growing health care problem, affecting 3% of women of childbearing age. AIM: This study attempted to systematically review the literature for 2000-2009 on pregnancy in CKD, as a guide for counseling. METHODS: Data sources included a Medline search for 2000-2009, employing MESH and free terms on pregnancy and CKD, limited to humans and English-language publications. Only studies observing at least 25 pregnancies were considered. The bibliographic search, abstract screening and data extraction were performed in duplicate. Out of over 3,000 references and 276 full texts, 23 studies fulfilled the selection criteria; 3 were added from references. RESULTS: The 26 studies reported on over 2,000 pregnancies. Five main categories were identified: CKD (399 pregnancies, excluding 2 population studies), lupus nephropathy (431 pregnancies), diabetic nephropathy (386 pregnancies), hematuria (310 pregnancies), kidney donors (586 pregnancies) and other. Definitions of diseases, outcomes and stratifications were nonhomogeneous, thus impairing meta-analytic pooling and quantification of the risks. Within these limits, 3 major qualitative determinants of outcome were confirmed as relevant in all subsets: CKD stage, hypertension and proteinuria. Their combination may multiply the interrelated major risks (for the mother: preeclampsia, renal function impairment and proteinuria; for the offspring: small babies, prematurity, death). Specifically, mothers with lupus nephritis have a relevant risk of death (1.15%), and share with diabetic nephropathy, the risk for perinatal death (up to 23% in lupus, 10% in diabetes). Malformations were not increased, except for urinary tract malformation in reflux nephropathy. CONCLUSIONS: There is a strong need to unify definitions and stratifications to allow quantitative evidence-based counseling for pregnant patients with CKD.

IVF twins have similar obstetric and neonatal outcome as spontaneously conceived twins: a prospective follow-up study.

Studies comparing the outcome of spontaneous versus IVF twin pregnancies report heterogeneous results. This may depend on differences in the studied populations and/or in the management approach to twin pregnancy. The aim of the present study was to compare both maternal and perinatal outcomes in dichorionic diamniotic twin pregnancies who where spontaneously conceived or originated by successful homologous IVF. In order to get homogeneous observations, monochorionic twin pregnancies and triplet pregnancies were excluded. Moreover, to avoid any possible bias deriving from differences in the obstetric management, all pregnancies were managed by the same team applying fixed obstetric protocols. The study included 223 twin pregnancies, 84 conceived by IVF and 139 spontaneously conceived. Overall, maternal and perinatal outcomes were similar in the two groups: no significant differences were observed as far as gestational age at delivery, birthweight, perinatal morbidity and mortality, and rate of malformations were concerned. The rate of Caesarean section was slightly, but not significantly, higher in IVF pregnancies. In conclusion, the outcome of IVF twin pregnancies is comparable to that of spontaneously conceived twin pregnancies, provided that the same management criteria are applied.