Placenta and maternal endothelium during preeclampsia: Disruption of the glycocalyx explains increased inositol phosphoglycans and angiogenic factors in maternal blood.

The etiology of the pregnancy syndrome preeclampsia is still unclear, while most hypotheses center on the placenta as the major contributor of the syndrome. Especially changes of the placental metabolism, including the use of glucose to produce energy, are important features. As an example, inositol phosphoglycan P-type molecules, second messengers involved in the glucose metabolism of all cells, can be retrieved from maternal urine of preeclamptic women, even before the onset of clinical symptoms. Alterations in the placental metabolism may subsequently lead to negative effects on the plasma membrane of the placental syncytiotrophoblast. This in turn may have deleterious effects on the glycocalyx of this layer and a disruption of this layer in all types of preeclampsia. The interruption of the glycocalyx in preeclampsia may result in changes of inositol phosphoglycan P-type signaling pathways and the release of these molecules as well as the release of soluble receptors such as sFlt-1 and sEndoglin. The release of placental factors later affects the maternal endothelium and disrupts the endothelial glycocalyx as well. This in turn may pave the way for edema, endothelial dysfunction, coagulation, all typical symptoms of preeclampsia.

Preeclampsia in 2023: Time for preventing early onset- and term preeclampsia: The paramount role of gestational weight gain.

The 2023 goal is to halve the incidence of preeclampsia worldwide to reach 3 million cases per year vs the current approximately 7 million cases. Preventive treatment by low dose aspirin only halves the incidence of early-onset preeclampsia (EOP < 34 weeks gestation) in high-risk women. However, 90% of PE cases are the late onset form (LOP, 34 weeks onward) proportionally associated with increasing maternal pre-pregnancy BMI. In 2018, we published a new method to calculate individualized optimal gestational weight gain based on normal Gaussian distribution of neonatal birthweights (SGA 10%, LGA 10%) and demonstrated that this optimal gestational weight gain (GWG) follows a linear equation suitable for all maternal PRE-pregnancy BMIs (from lean to obesities classes 1-2-3). A similar linear equation has been published recently based on a 2022 US database of 200,000 multiple pregnancies. Subsequently, we demonstrated in a prospective population study that in overweight and obese women who are able to achieve an optimal GWG, the rate of term preeclampsia (> 37 week's gestation) halves. Providing individual app-based calculations of optimal individual GWG, all patients will be aware of their personal weight gain target over the pregnancy. CONCLUSION: Halving the incidence of early-onset- and term preeclampsia worldwide by prevention is now theoretically achievable. Appropriate and timely start of low-dose Aspirin and providing women clear advice on their optimal GWG are they ingredients to achieve this goal.

Preface. 12th International Workshop Reunion island reproductive immunology, immunological tolerance and immunology of preeclampsia; 12-15 December 2022.

Overview of the discussions, 12th International Workshop Réunion island, Immunology and preeclampsia, December 2022.

Obesity class I and II and IOM 2009 gestational weight gain recommendations 5-9 kg. An audit on 10,000 term singleton deliveries.

OBJECTIVES: To compare several maternal-fetal morbidities comparing the Institute of Medicine IOM 2009 recommendations (IOMR: 5-9 kg in all obese women) between women with adequate gestational weight gain (GWG) and Inadequate (less than 5 kg), and excessive those gaining more than 9 kg among obese women class I (30-34.9 kg/m2) and class II (35-39.9 kg/m2). STUDY DESIGN: South-Reunion University's maternity (Reunion Island, Indian Ocean). 21-Year-observational cohort study (2001-2021). Epidemiological perinatal database with information on obstetrical and neonatal risk factors. MAIN OUTCOME MEASURES: Cesarean sections, preeclampsia, means birthweight, rate of small (SGA) or large (LGA) for gestational age newborns and macrosomic babies (≥4 kg). RESULTS: Among the singleton term live births (37 weeks onward) we could define the pre-pregnancy body mass index and GWG in 85.9% of cases. The final study population focused on 10,296 obese women (7138 obesity class I - 30-34.9 kg/m2, 3158 obesity class II - 35-39.9 kg/m2). Concerning inadequate GWG (less than 5 kg), respectively for obese I and II, IOMR babies were heavier (plus 90 and 104 g, p < .001), were more prone to be LGA OR 1.61 and 1.69, p < .001, macrosomic OR 1.49 and 2.21, p < .0001, IOMR women had more cesarean sections OR 1.33, OR 1.45, p = .001, and for obese II a tendency for more term preeclampsia OR 1.83, p = .06. CONCLUSION: This study demonstrates that for obese women these IOMR (5-9 kg) are mildly but significantly too high if we consider obesity class I and obviously too high for obesity class II (35-39.9 kg/m2).

The necessity to specify paternities in all obstetrical files in multigravidae.

OBJECTIVE: To compare in singleton multiparous pregnancies the effect of having a new father for an index pregnancy as compared with multiparas with the same male partner and primiparas. MATERIAL AND METHODS: 21 year data, 2001-2021, Reunion island. We compared 2233 multiparas who had a new partner NewPMP (cases) with 50,364 same partner multiparas samePMP (controls) and 30,741 primiparas. Paired t-test in for parametric, Mann-Whitney U test for non-parametric continuous variables. P-values < 0.05. RESULTS: As compared with primiparas, New paternity multiparas had similar neonatal outcomes: average birthweights 3044 g and 3017 g (vs 3125 g grams SamePMP, p < 0.0001), rates of low birthweights, very low birthweights (< 1500 g), rate of prematurity < 37 weeks, rate of early prematurity < 33 weeks and also "placental " intrauterine growth retardation, IUGR. Both primiparas and NewPMP had significant worse neonatal outcomes as compared with same partner multiparas for all these same items (all p < 0.05)). NewPMP had a much higher risk of preeclampsia than primiparas and samePMP (respectively, OR 1.74 and 2.9, p < 0.001), fetal deaths and perinatal mortality respectively, OR 1.4 and 1.8, p < 0.001. In 4 logistical models (primiparity, primipaternity, preeclampsia and "placental IUGR") new paternity multiparas had similar results compared with primiparas but very different results when compared with same partner multiparas. CONCLUSIONS: New paternity multiparas share with primiparas a significantly higher risk of perinatal and maternal morbidities than same partner multiparas. Paternity needs to be specified in all obstetrical files, perinatal databases- Health Registries.

Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to late-onset preeclampsia.

Among mammalian species, human reproduction has 2 outstanding features. The human hemochorial placentation is characterized by a very deep endovascular trophoblast invasion in the spiral arteries, reaching deep into the myometrium. This requires an agonistic direct cell-cell interaction between the maternal immune system and semiallogeneic trophoblast. The second feature is preeclampsia, a heterogeneous syndrome, a uniquely human condition. The human female is one of the few mammals exposed to her partner's semen on multiple occasions before conception. Regulatory T cells, especially paternal antigen-specific regulatory T cells, play an important role in the maintenance of pregnancy. Sexual intercourse increases the number of dendritic cells in the uterus that play an important role in the induction of paternal antigen-specific regulatory T cells. Paternal antigen-specific regulatory T cells maintain pregnancy by inducing tolerance. In the decidua basalis of preeclamptic cases, clonal regulatory T cells are reduced; these would normally monoclonally expand to recognize fetal or paternal antigens. Programmed cell death-1 expressed on T cells regulate cytotoxic T-cell activity and protect the fetus against maternal rejection. Programmed cell death-1 expression on clonal cytotoxic T cells is reduced in preeclampsia especially in early-onset preeclampsia, making the fetus and placenta vulnerable to attack by cytotoxic T cells. These phenomena can explain the epidemiologic phenomenon that preeclampsia is more common in couples using condom contraception, with shorter cohabitation periods, first pregnancies, first pregnancies in multiparous women when they change partner, and pregnancies after assisted reproduction using donated gametes. In contrast to its importance in early-onset preeclampsia, shallow trophoblast invasion does not play a role in the development of preeclampsia, that is, immune maladaptation does not seem to be involved. Late-onset preeclampsia (>34 weeks' gestation), representing 80% to 90% of preeclampsia in most developed countries with a "Western lifestyle," is strongly associated with maternal cardiometabolic variables (metabolic syndrome). Although the underlying pathophysiology might be quite different, syncytiotrophoblast stress is the final common pathway leading to the maternal syndrome among the subtypes of preeclampsia by causing an imbalance between proangiogenic factors (placental growth factor and vascular endothelial growth factor) and antiangiogenic factors (soluble fms-like tyrosine kinase-1 and soluble endoglin). Low-dose aspirin, started before 16 week's gestation, will prevent up to 60% of early-onset preeclampsia but will not prevent late-onset preeclampsia. Optimizing prepregnancy weight and controlling gestational weight gain may be the most effective ways to prevent preeclampsia.

Application of new fetal growth standards in a multiethnic population.

OBJECTIVES: Ultrasound assessment of fetal growth is essential to reduce adverse pregnancy outcomes. Intergrowth-21st developed international standards. Currently, we use in France chart based on Hadlock's formula. This study aims to evaluate, the impact of switching from national curves to IG-21 curves or a combination of IG-21 with Hadlock. METHODS: The study population consisted of 3 697 singleton pregnancies with fetal biometry measured between 22 and 38 weeks of gestation. Z-scores were calculated for each biometry according to CFEF and IG-21. The estimated fetal weight and its Z-score were calculated using the Hadlock formula and IG-21 formula. RESULTS: We observed 21% of head circumference, 9% of abdominal circumference and 7% of femoral length below the 10th centile with Intergrowth-21. Concerning estimated fetal weight, IG-21 classified 13.8% fetuses as SGA, IG-21/Hadlock 10.8% and CFEF 16.1%. Between 36 and 38 weeks of gestation, IG-21 classified more fetuses as SGA than IG-21/Hadlock and CFEF, respectively 18%, 14.1% and 13.3%. CONCLUSION: The use of IG-21 or IG-21/Hadlock in the general population would lower the number of fetuses classified as SGA except for fetuses between 36 and 38 weeks. During this period, many decisions of induced early delivery or specific management are established to prevent adverse perinatal outcome. Those results must be supplemented by a comparison to newborns' weight.

Admission into intensive care unit in preeclampsia: a four-year population-based study in Reunion Island.

INTRODUCTION: Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. The objective of our study was to study risk factors and complications associated with severe preeclampsia requiring intensive care unit (ICU) admission. METHODS: Retrospective comparative study over a period from 1st of January 2015 to 1st of January 2019 in the University's maternity unit of South Reunion (Indian Ocean). Our sampling included all preeclamptic patients who delivered in the Southern part of the island. Patients admitted to intensive care unit (ICU) and those who remained in the maternity unit (controls) were reviewed. RESULTS: Out of 482 preeclampsia cases, 94 women (19.5%) needed a transfer in ICU, of which only 21 (4.3%) needed invasive intensive care. Mean length of stay was 2.4 ± 2.1 days. ICU admission was associated with HELLP syndrome (OR 8.5 [4.9-14.9], p<.001), severe post-partum hemorrhage (OR 5.86 [1.29-26.70], p=.01) and early onset of preeclampsia (<34 weeks gestation), 2.97 [1.9-4.7], p<.001), leading to higher rate of C-section (OR 2.83 [1.67-4.78], p<.001). There were three patients with a history of eclampsia and no case of maternal death was reported. Fetal prognosis was much poorer in maternal ICU admissions than in controls, with outcomes including lower birth weight (1776 vs. 2304 g, p<.001) and higher perinatal morbidity (infant respiratory distress syndrome 3.70 [1.94-7.05], p<.001) and mortality (<.001). CONCLUSIONS: Women needing invasive ICU represented 4.3% of preeclampsia cases. This experience is of interest for lower resource settings such as in countries like Madagascar where very intensive ICU means are very poor, but simpler ICU surveillance is possible. Fetal prognosis was poor though no maternal death was reported. Thus, a multidisciplinary approach of patients with preeclampsia should be encouraged; admission into ICU should be facilitated, as soon as any sign of severity and complications appears.

The blurring boundaries between placental and maternal preeclampsia: a critical appraisal of 1800 consecutive preeclamptic cases.

OBJECTIVES: To present a comprehensive overview of different risk factors for early onset preeclampsia (<34 weeks gestation, EOP) vs. late onset (LOP). STUDY DESIGN: South-Reunion University's maternity (Reunion Island, Indian Ocean). 18.5 year-observational population-based cohort study (2001-2019). Epidemiological perinatal database with information on obstetrical and neonatal risk factors. All consecutive singleton pregnancies (>21 weeks) compared with all preeclamptic pregnancies delivered in the south of Reunion island. MAIN OUTCOME MEASURES: Comparing risk factors between EOP and LOP. RESULTS: Among 1814 singleton preeclamptic pregnancies (600 EOP and 1214 LOP), EOP women were older than LOP 29.5 vs. 28.6 years, p = .009, primigravidas (OR 0.78 [0.63-0.96], p = .02) were prone to LOP. History of preeclampsia (PE) (aOR 12.8 vs. 7.1), chronic hypertension (aOR 6.5 vs. 4.5) had much higher adjusted odds ratios for EOP than for LOP, p < .001. Specific to EOP: coagulopathies (aOR 2.95, p = .04), stimulated pregnancies (aOR 3.9, p = .02). Specific to LOP: renal diseases (aOR 2.0, p = .05) and protective effect for smoking (aOR 0.75, p = .008). EOP women were prone to have a lower BMI. CONCLUSION: "Placental preeclampsia" (defective placentation) being linked to early onset PE (<34 weeks gestation) while "maternal preeclampsia" (maternal cardiovascular predisposition) being typically manifesting as the late form of the disease LOP is not systematically verified. Future researches are needed to propose a more adapted paradigm.Highlights  Risk factors for different preeclampsia phenotypes (early/late); challenging proposed models.

Epidemiological evidence that severe obese women (pre-pregnancy BMI ≥40 kg/m2) should lose weight during their pregnancy.

OBJECTIVES: Defining the optimal gestational weight gain (optGWG) allowing to have "normal shaped" babies (10% of Small for gestational age, SGA, and10% of large LGA babies) in severe obese women (pre-pregnancy BMI ≥40 kg/m2). STUDY DESIGN: South-Reunion University's maternity (Reunion Island, Indian Ocean). 20 year-observational cohort study (2001-2019). Epidemiological perinatal data base with information on obstetrical and neonatal risk factors. All consecutive term (37-42 weeks gestation) singleton pregnancies (>21 weeks) live birth pregnancies delivered in the maternity. MAIN OUTCOME MEASURES: OptGWG to obtain newborns as close as possible of the 10% SGA/LGA goal for each BMI categories, 15-19.9, 20-24.9 …, as well as severe obese ≥40 kg/m2. RESULTS: Of the 71,318 singleton term live births (37 weeks onward), we could define the maternal pre-pregnancy body mass index and the GWG in of 61,764 patients (86.6%). Severe obese 40 kg/m2 losing 5-9.9 kg have 12.9% of LGA and 11.9% of SGA babies. Those losing 10 kg and more 12.7% of LGA and 7.3% of SGA. Our formerly proposed linear equation (validated from 15 to 40 kg/m2) may be prolonged at 45 kg/m2. opGWG(kg)=-1.2pp BMI(Kg/m2)+42±2kg. CONCLUSION: In our population, a 32 kg/m2 obese should gain 3.6 kg (instead of 5-9 kg, IOM 2009). A very obese 40 kg/m2 should lose 6 kg, and a severe obese 45 kg/m2 lose 12 kg.

Primipaternities and human birthweights.

OBJECTIVES: To investigate in singleton multiparous pregnancies the effect of having a new father for an index pregnancy on new-borns' birthweights and intrauterine growth restriction. DESIGN: 20 year-observational cohort study (2001-2020). SETTINGS: Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (French overseas department, Indian Ocean). MAIN OUTCOMES AND MEASURES: Comparing the 811 multiparas (cases) who had a new partner with the 49,712 who did not (controls), there were no differences concerning maternal age, education, ovulation induction/IVF, previous miscarriages, exams during pregnancies, pre-pregnancy BMI, gestational diabetes, and chronic hypertension. Cases had more previous pregnancies than controls (gravidity 4.2 vs 2.8, p < 0.001), volunteer abortions (OR1.93, p < 0.001), in vitro fecundations (OR 4.34, p < 0.001), were more likely to be unmarried (OR 2.94, p < 0.001) smoker (OR 2.2, p < 0.0001) and consuming alcohol during pregnancy (OR 2.35, p = 0.001). Cases had a much higher risk of preeclampsia than controls (OR 3.94, p < 0.001), especially early-onset preeclampsia (< 34 weeks) with an OR 4.1 (p < 0.001). Controlling for confounding factors (preeclampsia, smoking, alcohol use, early prematurity < 33 weeks, maternal ethnicity), primipaternity was an independent factor for small for gestational age newborns (OR 1.48, p < 0.001). CONCLUSIONS: It has been known for decades that primiparas have lighter babies than multiparas. Primipaternity represents also a risk for lower birth weights. Human birthweight seems to be linked with a "couple habituation" (to paternal genes) which may be not fully established in the first pregnancy of the couple.

Ethnic differences in postmaturity syndrome in newborns. Reflections on different durations of gestation.

OBJECTIVE: To describe the prevalence, by weeks of gestation, of post-maturity signs in newborns by ethnic origins. STUDY DESIGN: Observational cohort study (2001-2018), of all consecutive singleton births delivered at Center Hospitalier Universitaire Hospitalier Sud Reunion's maternity (Reunion Island, French overseas department, Indian Ocean). The presence of clinical post-maturity signs was recorded by a week of gestation using Clifford's clinical post-maturity signs in newborns (desquamation, dry skin, wrinkling fingers and cracked skin). RESULTS: Of the 67,463 singleton births during the period, 58,503 newborns were from Reunion island, 5756 were of European origin (mainland France), and 4061 newborns from the archipelago of Comoros (North of Madagascar). Mean duration of gestation was 276 days in Caucasian women, 272 days in Comorian mothers and 273 days in Reunionese (p < .001). Post-maturity is defined by WHO as gestation greater than 293 days (41 weeks + 6 days). At 41 weeks (287 days) 12.1% of Caucasian babies presented post-maturity signs and 22.4% meconium-stained liquid versus respectively, 22.8 and 27.1% in Reunionese and 44 and 39.8% in Comorians (p < .001). CONCLUSION: Among African (Black) pregnancies, duration of gestation was approximately 7 days shorter than in Caucasian (White) pregnancies. In the Reunionese intermixed population and Comorians, the gestation was shorter by 3-4 days. Black newborns presented severe clinical post-maturity signs beginning around 40 weeks and 4-6 days, while it was 1 week later in white infants. Consequences of these differences, with respect to clinical outcomes, are discussed.

Gestational weight gain and rate of late-onset preeclampsia: a retrospective analysis on 57 000 singleton pregnancies in Reunion Island.

OBJECTIVES: To investigate in singleton term pregnancies (≥37 weeks gestation) if applying optimal gestational weight gains (optGWG) on our population could have an effect on the incidence of late-onset preeclampsia (LOP). DESIGN: 18.5-year-observational cohort study (2001-2019). SETTINGS: Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (French overseas department, Indian Ocean), the only maternity providing services to take care of all preeclamptic cases in an area with approximately 360 000 inhabitants. MAIN OUTCOMES AND MEASURES: Simulation rates of LOP between women achieving optimal versus inappropriate GWG (insufficient and excessive) in the non-overweight, overweight and class I-III obesity categories. RESULTS: Among 66 373 singleton term pregnancies with a live birth, and 716 LOP (≥37 weeks, LOP37), the GWG could be determined in 87% of cases. In a logistic regression model validating the independent association of optGWG, maternal ages and body mass index (BMI), primiparity, smoking habit, chronic hypertension with term preeclampsia, optGWG reduced the risk of LOP37, aOR 0.74, p=0.004. Primiparity, higher maternal BMI, chronic hypertension and higher maternal age increased the risk of LOP37. The 'protective' effect of optGWG appeared stronger in patients with overweight and obesity in a linear manner: 0.57% versus 1.07% (OR 0.53, p=0.003), overweight; class I obese (30-34.9 kg/m²), 0.70% vs 1.56% (OR 0.44, p=0.01); severe obesity (≥35 kg/m²) 0.86% vs 2.55% (OR 0.33, p=0.06). All patients with overweight/obesity together, OR 0.42, p<0.0001. CONCLUSIONS: Overweight and obesity may not result in a higher risk of developing LOP at term when a optGWG is achieved. The results of this large retrospective population cohort study suggest that targeted and strictly monitored interventions on achieving an optGWG might represent an effective method to reduce the rate of LOP and would have the potential to halve its rate in women with overweight/obesity. These findings suggest a potentially achievable pathway to actively counterbalance the morbid effects of high BMIs, so we solicit adequately powered prospective trials.

Q fever seroprevalence in parturient women: the EQRUN cross-sectional study on Reunion Island.

BACKGROUND: Q fever (Coxiella burnetii infection) has been associated with adverse perinatal outcomes. After investigating the obstetrical importance of Q fever on Reunion island and demonstrating an association between incident Q fever and miscarriage, we conducted a cross-sectional serosurvey to assess the prevalence of Coxiella burnetii infection among parturient women. METHODS: Between January 9 and July 24, 2014, within the level-4 maternity of Saint Pierre hospital and the level-1 maternity of Le Tampon, we proposed to screen all parturient women for Coxiella burnetii serology. Seropositivity was defined using indirect immunofluorescence for a dilution of phase 2 IgG titre ≥1:64. Further dilutions were chosen to discriminate recent or active infections from past or prevalent infections (< 1:128) and classify these as either possible (1:128), or probable (≥1:256). Recurrent miscarriage, stillbirth, preterm birth, small-for-gestational as well as a composite outcome of these adverse pregnancy outcomes were compared according to seropositivity using bivariate analysis or propensity score matching of seropositive and seronegative women on confounding factors. RESULTS: Among 1112 parturient women screened for Q fever over this 7-month period, 203 (18.3%) were seropositive. Overall weighted seroprevalence was of 20.1% (95%CI, 17.7-22.5%). Weighted seroprevalence of probable infections was 4.7% (95%CI 3.4-5.9%), while > 90% of positive serologies corresponded to past infections or false positives. Seropositivity was associated with none of the abovementioned adverse perinatal outcomes, whether in unpaired or matched analyses on propensity score. CONCLUSION: The magnitude and the pattern of seroprevalence suggest that Q fever is endemic on Reunion island. In this context, we found no significant contribution of prevalent Coxiella burnetii infection to adverse pregnancy outcomes. Although reassuring, these data put in our endemic context, with a previously demonstrated increased risk of incident Q fever associated miscarriage, encourage us to protect pregnant women against the risk of new infection, periconceptional or early in pregnancy.

Validation of the 34-week gestation as definition of late onset preeclampsia: Testing different cutoffs from 30 to 37 weeks on a population-based cohort of 1700 preeclamptics.

INTRODUCTION: Early onset preeclampsia (EOP) and late onset preeclampsia (LOP) have been differentiated with a cut-point of ≤34 weeks. This classical definition has never been examined with respect to maternal characteristics by different gestational age cut-points. We examined maternal characteristics in a population-based cohort of 1736 preeclamptic deliveries at different gestational age cut-points from 30 to 37 weeks (CO30 to CO37). MATERIAL AND METHODS: Eighteen-year observational population-based historical cohort study (2001-2018). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity. Standardized epidemiological perinatal database. RESULTS: The incidence of EOP was lower in adolescents (1.8% vs 3.5%, odds ratio [OR] 0.50, P = .17). Conversely, the odds of LOP was increased for women over 35, beginning at C030 (OR 1.13, P = .02) and this effect (OR = 1.2) was still detectable at C037 (P = .06). Among primigravid women, the incidence of EOP was lower than LOP (OR ranging from 0.71 to 0.82 for different CO). Conversely, the incidence of LOP was higher (adjusted OR about 2.7 [CO30-CO34] with a rise to 3.3 at CO37 (P < .001). Women with EOP had a lower body mass index (BMI) as compared with LOP at CO34 and CO37. The adjusted OR (per 5 kg/m2 increment) declined from 1.06 to 1.03 from CO30 to C037 in EOP women. Conversely, for LOP, the adjusted odds ratio (aOR) increased from 1.04 to 1.06 from CO30 to CO37 (P < .001). Gestational diabetes mellitus was not associated with LOP at any cut-off (aOR 1.07, NS) but was protective against EOP from CO30 to CO34 (aOR 0.42, 0.61 and 0.73, respectively, P < .001). This protective effect disappeared at CO37. Chronic hypertension and history of preeclampsia were both EOP and LOP risks but with a much stronger effect for EOP (chronic hypertension: aOR 6.0-6.5, history of preeclampsia: aOR 12-17). CONCLUSIONS: The 34th week of gestation appears to provide a reasonable cut-point to differentiate between EOP and LOP. Additional research is needed to better describe the possible differences in the pathophysiology of these different phenotypes.

Discordant malformations in monochorionic twins: a retrospective cohort study in La Reunion Island.

Background: Discordant malformation between monochorionic twins is a rare and unknown phenomenon.Objectives: To estimate the incidence of discordant monochorionic twins and to describe their characteristics.Study design: A retrospective multicenter cohort of pregnancies between 2002 and 2015 in La Reunion Island was analyzed, thanks to a population-based register. Only monochorionic pregnancies were included in order to analyze specifically monozygotic twins. We defined as discordant twin pairs those in which different malformations were identified for each twin and those with only one fetus showing a malformation.Results: During the study period, 203,807 births occurred, including 410 monochorionic twin pairs. Congenital anomalies rate for monochorionic twin pairs was 10.7%. We included 38 monochorionic twin pairs with discordant phenotypes, which represent 9.3% of monochorionic twin pairs and 86.4% of monochorionic twin pairs affected by congenital anomalies. Among them, both twins were affected by different congenital anomalies in 7 pairs (18.4%), and only one twin was affected in 31 pairs (81.6%). We identified 20 congenital heart anomalies (44.4%), 5 brain anomalies (11.1%), 5 genital anomalies (11.1%), 4 axial bones and skull anomalies (8.9%), 4 limb anomalies (8.9%), 4 facial anomalies (8.9%), 3 urological anomalies (6.6%), 2 thoracic anomalies (4.4%), 1 bile duct anomaly (2,2%), 1 abdominal parietal defect (2.2%), and 1 aneuploidy (2.2%). Among them, 3 (6.6%) fetuses had an association of malformations. Among the 45 fetuses with malformations, 37 fetuses (82.2%) were born alive and 21 (46.6%) had postnatal surgery.Conclusions: Despite a supposed identical genome, discordant congenital anomalies in monochorionic twin pregnancies are not exceptional and related to genetic and epigenetic mechanisms. Sonographers and pediatricians should know that in monochorionic twin a pair, the occurrence of discordant phenotypes is high (9.3%).

The burden to be second twin: a population-based study of 2686 twins: (2124 dichorionic). Proposal of the concept of mobility.

Objectives: To identify if there is a specific neonatal morbidity/mortality among second twins relative to first twins.Study design: A 17-year (2001-2017) population-based observational cohort of all twin newborns born in the South of Reunion island after 21 weeks.Results: Among 1062 dichorionic (DTP) and 281 monochorionic twin pregnancies (2686 newborns), twin 2 have a doubled risk to be in breech presentation and a bad Apgar at 1 mn (≤6) in vaginal deliveries. Specific to dichorionic pregnancies, twin 2 were lighter by 50-60 g than twin 1, had higher rates of intrauterine growth retardation (IUGR), OR 1.33, p = .007, a doubled risk to have congenital abnormalities OR 2.1, p = .006.Conclusion: In dichorionic twin pregnancies, second twins having a doubled prevalence of severe congenital abnormalities are not completely elucidated and deserves further research. (1) We propose that twin 2 presenting higher risks of being IUGR and much higher risks of severe malformations suggest that during pregnancy, the less mobile of the two twins is "relegated" to the back of the uterus. (2) For interventions in the delivery room, systematically the most experimented neonatologist should plan to manage the second twin because significantly twin 2 presents higher problems than twin 1.