Miha Lucovnik

Risk factors for preeclampsia in twin pregnancies: a population-based matched case-control study.

Abstract Objective: To evaluate associated factors for preeclampsia in twin gestations and to compare incidences of pregnancy complications among twin pregnancies with vs. without preeclampsia. Patients and methods: We performed a case-control study using a population dataset of twin pregnancies delivered after 24 weeks of gestation, in Slovenia, between 1997 and 2009. Cases were twin gestations complicated by preeclampsia and controls were cases matched by gestational age, parity, and chorionicity. Results: We identified 181 cases (4.7%) of preeclampsia among 3885 twins and 542 matched controls. High pre-pregnancy body mass index (BMI) and gestational diabetes were significantly associated with preeclampsia [odds ratio (OR) 1.8, 95% CI 1.26, 2.77 for overweight (BMI 25.0–29.9); OR 4.72, 95% CI 2.83, 7.89 for obese (BMI≥30), and OR 2.19, 95% CI 1.03, 4.68 for gestational diabetes]. The association was not significant for preexisting hypertension, maternal age, smoking, and pregnancy following assisted reproduction. Placental complications (previa, abruption, or adherent placenta) were more common, and low birth weight less common in the preeclampsia group (P=0.03 and P=0.01, respectively). Conclusions: High pre-pregnancy BMI carries an especially high risk for the development of preeclampsia and its complications in twin gestation.

Impact of pre-gravid body mass index and body mass index change on preeclampsia and gestational diabetes in singleton and twin pregnancies

Abstract Objective: To examine pre-gravid body mass index (BMI) and gestational BMI change impact on preeclampsia and gestational diabetes mellitus (GDM). Methods: Retrospective population-based cohort study. Data from Slovenian National Perinatal Information System were analyzed for the period 2002–2011. Three singleton controls were matched by parity and maternal age to each twin pregnancy delivered at >36 weeks. Student’s t test was used to compare pre-gravid BMI and gestational BMI change in different groups (p < 0.05 significant). Results: 2046 twin and 6138 singleton pregnancies were included. Twin and singleton patients with preeclampsia or GDM had higher pre-gravid BMI (p < 0.001). Gestational BMI change was smaller in twins with GDM (p < 0.001), and not associated with preeclampsia (p = 0.07). Smaller gestational BMI change in singleton pregnancies was associated with GDM (p < 0.001), and greater BMI change with preeclampsia (p = 0.004). Conclusions: Pre-gravid BMI is more strongly associated with preeclampsia and GDM in twin and singleton pregnancies than gestational BMI change. Smaller gestational BMI change in GDM pregnancies reflect the importance of dietary counseling.

Changes in incidence of iatrogenic and spontaneous preterm births over time: a population-based study

Abstract Objective: To examine the proportion of iatrogenic births among all preterm births over a 26-year period. Patients and methods: A registry-based survey of preterm deliveries between 1987 and 2012 analyzed by the onset of labor: spontaneous with intact membranes, preterm premature rupture of membranes (PPROM) or iatrogenic. Stratification into categories by gestation (22 weeks to 27 weeks and 6 days, 28 weeks to 31 weeks and 6 days, 32 weeks to 33 weeks and 6 days, 34 weeks to 36 weeks and 6 days) was performed. Preterm birth rates were analyzed using the Mantel-Haenszel linear-by-linear association χ2-test (P<0.05 significant). Logistic regression was used to account for potential confounders. Results: Overall preterm birth rate was 5.9% (31328 deliveries) including 2358 (0.4%) before 28 completed weeks, 3388 (0.6%) between 28 weeks and 31 weeks 6 days, 3970 (0.8%) between 32 weeks and 33 weeks and 6 days, and 21611 (4.1%) between 34 weeks and 36 weeks and 6 days There was an increase in overall preterm birth rate (P<0.001). The rate of iatrogenic preterm births and PPROM increased over time (P<0.001 and P<0.014, respectively). Rates of spontaneous preterm birth decreased (P<0.001). After accounting for potential confounders, year of birth remained an independent risk factor for iatrogenic preterm delivery in all four gestational age categories (P<0.001). Conclusion: The incidence of iatrogenic preterm birth is increasing with a concomitant decrease in the incidence of spontaneous preterm birth. Attempts to analyze, interpret and decrease preterm birth rates should consider spontaneous and iatrogenic preterm births separately.

Maternal obesity in singleton versus twin gestations: a population-based matched case–control study

Abstract Objective: To examine the impact of pre-pregnancy obesity on adverse outcomes in twin compared to singleton pregnancies. Methods: Dichorionic twin gestations with maternal body mass index >30 were matched to three singleton controls. Both obese groups were matched (1:3) with non-obese controls. Rates of preeclampsia, gestational diabetes, cesarean section, and preterm birth were compared. Results: One hunder eighty-nine dichorionic twin pregnancies in obese mothers were matched to 567 twin pregnancies in non-obese mothers, and to 567 singleton pregnancies in obese mothers. The latter were matched to 1701 non-obese mothers with singletons. Preeclampsia was more common in obese mothers with both twins and singletons (odds ratio (OR) 3.95, 95% confidence interval (CI) 2.18–7.16 and OR 6.53, 95% CI 3.75–11.4, respectively) as was gestational diabetes (OR 4.35, 95% CI 2.18–8.69; OR 5.53 95% CI 3.60–8.50). Obese mothers with singletons were more likely to deliver abdominally, but the cesarean rates were obesity independent in twins. Obese mothers were more likely to deliver at < 34 weeks in both twin and singleton groups (OR 1.65, 95% CI 1.10–2.48, and OR 2.41, 95% CI 1.21–4.77, respectively). Conclusion: Obesity-attributable adverse outcomes are lower in twins compared to singletons. Obesity increases the risk of preterm birth regardless of plurality.

Neutrophil defensins but not interleukin-6 in vaginal fluid after preterm premature rupture of membranes predict fetal/neonatal inflammation and infant neurological impairment.

Objective. To determine whether neutrophil defensins (HNP1–3) and interleukin‐6 (IL‐6) in vaginal fluid after preterm premature rupture of membranes predict fetal inflammatory response syndrome (FIRS), neurological impairment or chorioamnionitis. Design. Prospective study. Setting. Tertiary referral university hospital. Population. Forty‐two patients with preterm premature rupture of membranes at <32 weeks. Methods. Levels of HNP1–3 and IL‐6 were measured in vaginal fluid obtained by swabs. Mann–Whitney U‐test was used to compare HNP1–3 and IL‐6 levels in groups with vs. without FIRS, infant death or neurological impairment, and chorioamnionitis (p<0.05 significant). Logistic regression was used to control for potential confounders. Diagnostic accuracies of HNP1–3 and IL‐6 were determined by receiver operator characteristics analysis. Main Outcome Measures. Fetal inflammatory response syndrome was defined as neonatal inflammation within 72hours postpartum. Neurological impairment was defined as motor and/or tone abnormalities at one year of corrected age. Chorioamnionitis was diagnosed histologically. Results. Levels of HNP1–3, but not IL‐6, were higher in 12 cases of FIRS (p=0.019 and p=0.256, respectively). Levels of HNP1–3, but not IL‐6, were higher in 14 cases of infant death or neurological impairment (p=0.015 and p=0.100, respectively) and, when only survivors were analyzed, in nine cases of neurological impairment (p=0.030 and p=0.187, respectively). Levels of HNP1–3 and IL‐6 were higher in 29 cases of chorioamnionitis (p=0.005 and p=0.003, respectively). The differences remained significant after adjustment for gestational age. Levels of HNP1–3 predicted FIRS, infant death or neurological impairment and chorioamnionitis with an area under the curve of 0.75, 0.79 and 0.78, respectively. Conclusions. Elevated vaginal fluid HNP1–3 and IL‐6 levels are associated with histological chorioamnionitis. Elevated HNP1–3 can also identify FIRS and predict infant death or neurological impairment.

No “masculinization” effect of a male on birth weight of its female co-twin

Abstract Objective: To test the hypothesis that the presence of a male affects birth weight of its female co-twin. Patients and methods: We evaluated a large population dataset of bichorionic twins after exclusion of potential confounders and after controlling for parity and gestational age. We tested the hypotheses that males (M) are heavier than females (F) irrespective of gender mix, parity and gestational age, and the hypothesis that birth weight of twins might be influenced by the gender of the co-twin. Results : There were 819 MM pairs, 777 FF pairs and 1097 MF sets, for a total of 2735 males and 2651 female twins. Male twins were heavier than female twins, irrespective of parity or gestational age; twins born to multiparas were heavier than twins born to nulliparas, except for very preterm births (≤32 weeks); males from MF pairs were heavier than males from MM pairs, but the mean birth weight of females from MF was not different from that of females from FF sets suggesting no “masculinization” effect of the male on birth weight of its female co-twin, irrespective of parity and gestational age. Conclusions: After exclusion of potential confounders and controlling for chorionicity, parity, and gestational age, our data do not support the presence of a “masculinization” effect on birth weight.

Lung and cardiac ultrasound for hemodynamic monitoring of patients with severe pre-eclampsia

To evaluate lung and cardiac ultrasound for the assessment of fluid tolerance and fluid responsiveness before and after delivery in pregnant women with severe pre‐eclampsia (PE).

Assessment of Parturition with Cervical Light-Induced Fluorescence and Uterine Electromyography

Parturition involves increasing compliance (ripening) of the uterine cervix and activation of the myometrium. These processes take place in a different time frame. Softening and shortening of the cervix starts in midpregnancy, while myometrial activation occurs relatively close to delivery. Methods currently available to clinicians to assess cervical and myometrial changes are subjective and inaccurate, which often causes misjudgments with potentially adverse consequences. The inability to reliably diagnose true preterm labor leads to unnecessary treatments, missed opportunities to improve neonatal outcome, and inherently biased research of treatments. At term, the likelihood of cesarean delivery depends on labor management, which in turn depends on accurate assessments of cervical change and myometrial contractility. Studies from our group and others show that noninvasive measurements of light-induced fluorescence (LIF) of cervical collagen and uterine electromyography (EMG) objectively detect changes in the composition of the cervix and myometrial preparedness to labor and are more reliable than clinical observations alone. We present a conceptual model of parturition constructed on cervical LIF and uterine EMG studies. We also explore how these methodologies could be helpful with managing patients experiencing preterm contractions and with optimizing labor management protocols aimed to reduce cesarean section.

Hypertensive disorders during monozygotic and dizygotic twin gestations: A population-based study

ABSTRACT Objective: To determine whether the incidence of hypertensive disorders is different in monozygotic compared to dizygotic twin pregnancies. Methods: A registry-based survey of twin pregnancies delivered during 2003 to 2012. We used the best clinical estimate of zygosity based on the concept that all monochorionic twins are monozygotic and all unlike-sex pairs are dizygotic, thus excluding same-sex dichorionic twin gestations for which zygosity cannot be ascertained on clinical grounds. Study cohorts were twin pregnancies with or without preeclampsia and gestational hypertension. Results: A total of 3419 twin gestations met the inclusion criteria, of which 442 (12.9%) were monochorionic and 1255 (36.7%) were unlike-sex twins, excluding 1722 same-sex dichorionic twin gestations (50.4%). There was no significant difference in the incidence of preeclampsia (OR: 0.9; 95% CI: 0.4–2.0 for monozygotic males and OR: 0.6; 95% CI: 0.3–1.4 for monozygotic females) and gestational hypertension (OR: 0.7; 95% CI: 0.2–2.5 for monozygotic males, and OR: 0.7; 95% CI: 0.2–2.3 for monozygotic females) between monochorionic and unlike-sex pairs. Maternal prepregnancy obesity and nulliparity were the only significant associated factors of preeclampsia (OR: 3.8; 95% CI: 2.0–7.0, and OR: 2.5; 95% CI: 1.4–4.4, respectively). Maternal prepregnancy obesity (OR: 5.5; 95% CI: 2.5–12.2), maternal age ≥36 years (OR: 2.5; 95% CI: 1.1–6.1), and family history of hypertension (OR: 2.6; 95% CI: 1.3–5.1) were significantly associated with gestational hypertension. Conclusion: Based on a large population-based dataset and on the best clinical estimate of twin zygosity, it appears that zygosity is not associated with hypertensive disorders in twin gestations.

A dose?response relation exists between different classes of pre-gravid obesity and selected perinatal outcomes

ObjectiveTo examine if a “dose–response” relation exists between different classes of pre-gravid obesity and selected perinatal outcomes.MethodsWe evaluated 16,566 obese mothers, including 12,064 (72.8%), 3410 (20.6%), and 1092 (6.6%) with obesity class I, II, and III, respectively. We compared maternal age, primiparity, gestational age at birth, birth weight, GDM, hypertensive disorders, and the incidence of cesarean sections.ResultsThere was a significantly increased incidence (from class I to class III) for GDM (8.5–14.4%), chronic hypertension (2.8–9.0%), gestational hypertension (6.7–14.2%), and for preeclampsia (5.3–9.3%). No such relationship existed for birth weight and gestational duration.ConclusionClasses of obesity during pregnancy exhibit a “dose–response” relationship with maternal morbidity, but no such relationship was found with pregnancy duration and birth weight.