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.

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.

Pregnancy outcomes of Q fever: prospective follow-up study on Reunion island.

BACKGROUND: Q fever has been associated with perinatal complications. We conducted a prospective follow-up study to assess both the incidence of adverse pregnancy outcomes (APOs) associated with Coxiella burnetii infection and the contribution of Q fever to APOs. METHODS: Between May 1 and October 31, 2013, within the regional perinatal health care centre of Saint Pierre, Reunion island, we investigated unexplained miscarriages, stillbirths, preterm births or small-for-gestational age children. Seropositivity for C. burnetii antibodies was defined using indirect immunofluorescence for a phase 2 IgG titre ≥1:64. Acute Q fever was defined for a high phase 2 IgG titre ≥1:256 (compatible with recent or active infection) or the detection of C. burnetii genome in miscarriage products and placentas. Incidence rate ratios (IRR) for Q fever related APOs (taken as a composite outcome or individually) were assessed using Poisson regression models for dichotomous outcomes controlling major confounders. RESULTS: Over a 6-month period, 179 pregnant women suspected or diagnosed with an APO were investigated for Q fever, of whom 118 met the definition for an APO. Of these, 19 were seropositive and 10 presented a profile indicative of an acute infection. For three women with an acute Q fever, the chronology between the onset of infection, the APO (2 miscarriages, 1 preterm birth) and the seroconversion suggested causality in the pathogenesis. The cumulative incidence of Q fever related APOs was estimated between 2.2‰ and 5.2‰, whether causality was required or not. Both C. burnetii exposure and acute Q fever were independently associated with APOs (IRR 1.55, 95% CI 1.31-1.84; IRR 1.47, 95% CI 1.15-1.89, respectively). CONCLUSIONS: In the endemic context of Reunion island, acute Q fever may lead to APOs. To limit the burden of Q fever on reproduction, pregnant women should be kept away from farms and avoid direct contact with ruminants.

Mortality and severe morbidity of very preterm infants: comparison of two French cohort studies.

BACKGROUND: In Reunion Island, a French overseas department, the burden of preterm birth and perinatal mortality exceed those observed in mainland France, despite similar access to standard perinatal care. The purpose of the study was to compare the outcome of two cohorts of NICU-admitted very preterm infants born between 24 and 31 weeks of gestation (WG): the registry-based OGP (Observatoire de la Grande Prématurité, Reunion Island, 2008-2013) cohort, and the nationwide EPIPAGE-2 (mainland France, 2011) observational cohort. METHODS: The primary outcome was adverse neonatal outcomes defined as a composite indicator of in-hospital mortality or any of three following severe morbidities: bronchopulmonary dysplasia (BPD), necrotising enterocolitis, or severe neurological injury (periventricular leukomalacia or grade III-IV intraventricular haemorrhages). Logistic regression modelling adjusting for confounders was performed. RESULTS: A total of 1272 very preterm infants from the Reunionese OGP cohort and 3669 peers from the mainland EPIPAGE-2 cohort were compared. Adverse neonatal outcomes were more likely observed in the OGP cohort (32.6% versus 26.6%, p <  0.001), as result of both increased in-hospital mortality across all gestational age strata and increased BPD among the survivors of the 29-31 WG stratum. After adjusting for gestational age, gender and multiple perinatal factors, the risk of adverse neonatal outcomes was higher in the OGP cohort than in the EPIPAGE-2 cohort across all gestational age strata. CONCLUSIONS: Despite similar guidelines for standard perinatal care, very preterm infants born in Reunion Island have a higher risk for death or severe morbidity compared with those born in mainland France.

Nutrition practice, compliance to guidelines and postnatal growth in moderately premature babies: the NUTRIQUAL French survey.

BACKGROUND: The nutritional care provided to moderately premature babies is poorly studied. For a large cohort of such babies, we aimed to describe: nutrition practice intentions, comparison of the intended with the actual practice, compliance of actual practice to current nutrition guidelines, and postnatal growth. METHODS: A questionnaire was sent out to 29 neonatal intensive care units in France, in order to address practice intentions. In the same units, retrospective patient's data were collected to assess actual practice, compliance to nutrition guidelines and infant postnatal growth. The cumulative nutritional deficit during the two first weeks of life was calculated and variables associated with ΔZ-score for weight at 36 weeks postconceptional age/discharge (ΔZ-score(w) 36PCA/DC) were analysed by multivariate linear regression. RESULTS: 276 infants born 30 to 33 weeks of gestation were studied. Among them, 76% received parenteral nutrition on central venous line after birth. On day of life 1 (DOL1), 93% of infants had parenteral amino acids (AA), at an intake ≥ 1.5 g/kg in 27% of cases. Lipids were started at ≤ DOL2 in 47% of infants. There was a divergence between the intended and the actual practice for both AA and lipids intake. The AA and energy cumulative deficit (DOL1 to DOL14) were respectively 10.9 ± 8.3 g/kg and 483 ± 181 kcal/kg. Weight Z-score (mean ± SD) significantly decreased from birth (-0.17 ± 0.88) to 36 weeks PCA/DC (-1.00 ± 0.82) (p < 0.0001), and the extra-uterine growth retardation (EUGR) rate at 36 weeks PCA/DC was 24.2%. Independent variables associated with ΔZ-score(w) 36PCA/DC were AA cumulative intake and DOL of full enteral feeding. CONCLUSIONS: Nutrition intake was not in compliance with recommendations, and the rate of EUGR was considerable in this cohort. Efforts are needed to improve adherence to nutrition guidelines and growth outcome of moderately preterm infants.

Clear amniotic fluid aspiration syndrome: A novel description of an old entity.

BACKGROUND: Clear amniotic fluid aspiration syndrome (CAF-AS) is a very rare event occurring in 0.25% of our term clear amniotic fluids deliveries. The study's aims were: 1. to characterize the risk factors and outcomes associated with Clear Amniotic Fluid Aspiration Syndrome and 2. to compare the outcomes of Clear Amniotic Fluid Aspiration to Meconium Aspiration. METHODS: This was an observational study over a 22-year period in a single level-3 medical center. Compared were parturient/labor characteristics and neonatal outcomes in cases with suspected Clear Amniotic Fluid Aspiration to cases suspected for Meconium Aspiration. RESULTS: Out of 79,620 term deliveries there were 66,705 (83.8%) clear amniotic fluids and 12,915 (16.2%) meconium stained amniotic fluid (MSAF). Of neonates born with clear amniotic fluid, 166 (0.25%) were diagnosed with Clear Amniotic Fluid Aspiration Syndrome (CAF-AS), while 202 (15.7%) of those born with MSAF, were diagnosed with aspiration syndrome (MSAF-AS). Both conditions had comparable rates of mild manifestation (67.5% vs 69.2%, p = 0.63). Persistent pulmonary hypertension (PPH) occurred 5 times less in CAF-AS than MSAF-AS (4% vs 20%, OR 0.17, P< 0.0001) Both conditions presented similar rates of surfactant without PPH (11.1% vs 13.4%, p = 0.87). There was 1 postnatal death in CAF-AS vs 10 in MSAF. CONCLUSION: CAF-AS were quantitatively quite similar in terms of need of actual active intervention of the neonatologists in the delivery room (166 vs 202, i.e. in terms of numbers of cases and not prevalence) to MSAF-AS.We identified in these cases two major specific causes: hyperkinetic explosive deliveries in multiparas and long-lasting episodes of maternal hypotension due to epidural/spinal anaesthesia during labor. Out of 140 million births per year in the world, it should be of concern that 3 million cases are neglected nowadays. Future studies should evaluate if this CAF-AS should benefit from a more active intervention such as immediate endotracheal suction at birth, this clear fluid being very easy to suction.

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).

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.

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.

Congenital heart defects in La Réunion Island: a 6-year survey within a EUROCAT-affiliated congenital anomalies registry.

OBJECTIVES: This study compares the prevalence and perinatal mortality of congenital heart defects on La Réunion with European (EUROCAT) standards. METHODS AND RESULTS: Data were extracted from a EUROCAT-affiliated congenital malformations registry, covering 88,025 births during the period 2002-2007, on the whole island territory. A total of 512 congenital heart defects were registered, including 424 live births, 18 foetal deaths from 16 weeks of gestation, and 70 terminations of pregnancy. The total prevalence of congenital heart defects was 5.8 per 1000 births and live birth prevalence was 4.8 per 1000. The total prevalence of non-chromosomal congenital heart defects was 5.1 per 1000 births, of which 3% were perinatal deaths, 33.3% prenatally diagnosed, and 11.6% termination of pregnancy. Severe non-chromosomal congenital heart defects - excluding ventricular septal defects, atrial septal defects, and pulmonary valve stenosis - occurred in 2.1 per 1000 births, of which 10.3% were perinatal deaths, 59.1% prenatally diagnosed, and 24.3% termination of pregnancy. Of the severe congenital heart defects, the rates of single ventricle (0.20‰), Ebstein anomaly (0.11‰), common arterial trunk (0.25‰), and atrioventricular septal defect (0.62‰) exceeded averages found in Europe, although coarctation of the aorta was infrequent. Conversely, rates of ventricular septal defects, atrial septal defects, and pulmonary valve stenosis were inferior to European standards. Slightly less than half of the congenital heart defects of chromosomal origin were associated with Down syndrome. CONCLUSION: In La Réunion, the total prevalence of congenital heart defects is far inferior to that found in Europe. The difference can be attributable to lower prevalences of mild congenital heart defects.

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.

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.

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.

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.

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.