Perinatal outcome and long-term hospitalization of triplets according to birth order.

PURPOSE: The association between birth order and adverse perinatal outcomes has been well studied in twin pregnancies. However, little is known about the differences in immediate perinatal outcomes as well as long-term hospitalization of the offspring in triplet pregnancies according to their birth order. As such, we aimed to assess the differences in immediate perinatal outcomes and long-term hospitalizations among triplets by their birth order. METHODS: In a retrospective hospital-based cohort study, immediate perinatal outcomes and long-term hospitalizations were compared among triplet siblings according to their birth order. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. The study groups were followed until 18 years of age for cardiovascular, respiratory, neurological, and infection-related hospitalizations. Generalized estimation equation (GEE) models were used to control for confounders. Kaplan-Meier survival curves were used to compare cumulative long-term hospitalization incidences and Cox proportional hazards models were performed to control for confounders. RESULTS: The study included 117 triplet deliveries. Rates of small for gestational age (SGA) infants increased linearly by birth order (6.0%, 7.7%, and 15.4% for the first, second, and third siblings, respectively; p-value for trends = 0.035). Using a GEE model controlling for maternal age, being born third in a triplet pregnancy was independently associated with SGA (third vs. first sibling, adjusted OR 3.0, 95% CI 1.38-6.59, p = 0.005). No significant differences in cardiovascular, respiratory, neurological, and infection-related hospitalizations were noted among the first, second, and third siblings. Likewise, using Kaplan-Meier survival analyses, no significant differences in the cumulative incidence of long-term pediatric hospitalizations were noted between the siblings. In Cox proportional hazards models, controlling for weight and gender, birth order in a triplet pregnancy did not exhibit an association with long-term hospitalizations of the offspring. CONCLUSION: Despite the association between birth order and SGA, birth order in triplets does not seem to have an impact on the risk for long-term offspring hospitalization.

[GESTATIONAL WEIGHT GAIN AND LONG-TERM POSTPARTUM WEIGHT RETENTION].

INTRODUCTION: Pregnant women have been told that gaining weight during pregnancy is important for maternal and perinatal health outcomes. However, today it is known that excessive weight gain during pregnancy is associated with adverse health outcomes. This article presents the connection between gestational weight gain and long-term postpartum weight retention as well as relevant epidemiology, predictors for postpartum weight retention and implications of its occurrence. In addition, in this review we raise possible prevention and intervention strategies for preventing weight retention following delivery. Maintaining proper weight gain after delivery, supported by appropriate prevention and intervention for postpartum weight retention, such as counseling regarding a healthy diet and physical activity, social support for postpartum women and social awareness for this important issue can aid in reducing the possible complications of future weight retention.

Unfolding the pathophysiology of congenital thrombotic thrombocytopenic purpura in pregnancy: lessons from a cluster of familial cases.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a rare, potentially life-threatening thrombotic microangiopathy, manifests either as congenital TTP or acquired forms. It is caused by the absence or severe depletion of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) protease, leading to the accumulation of ultra large von Willebrand factor multimers as well as extensive platelet adhesion and clumping, which can ultimately cause severe secondary end-organ damage. Pregnancy can provoke or exacerbate TTP, leading to maternal and fetal complications. OBJECTIVE: In this report, we focused on pregnancy outcomes in a recently recognized cohort of congenital TTP patients of Bedouin Arab descent in southern Israel who were all homozygous for a novel c.3772delA variant of the ADAMTS13 gene, leading to the clinical manifestations of TTP largely during pregnancy. STUDY DESIGN: All patients presented in this study belong to 2 closely related families of Arab Bedouin descent and were found to be homozygous for a novel ADAMTS13-c.3772delA variant. The cohort consisted of 19 females; 16 of them had congenital TTP and had been pregnant and were thus included. Patient data were collected from electronic medical records. RESULTS: Of note, 13 women from our cohort, who delivered 14 fetuses (owing to 1 twin pregnancy), were diagnosed with congenital TTP following complicated pregnancies, which included recurrent pregnancy loss, stillbirth, early onset preeclampsia (both mild and severe), hemolysis, elevated liver enzymes and low platelet count syndrome, intrauterine growth restriction with abnormal Doppler flow, preterm premature rupture of membranes, and a total perinatal mortality rate of 30.7% (4/13). An additional 3 women, who were diagnosed owing to complications outside of pregnancy and at older ages, experienced TTP during their pregnancies, which occurred before diagnosis. Subsequent pregnancies were treated with fresh frozen plasma leading to a 100% fetal survival rate in the pregnancies that reached fetal viability. All placentas had lesions consistent with maternal vascular underperfusion. However, the severity and frequency of these lesions were lower in the 8 placentas from pregnancies treated with fresh frozen plasma. CONCLUSION: This case series details a distinctive cohort of congenital TTP patients, all homozygous for the same, novel ADAMTS13 variant, who presented with clinical complications during pregnancy and maternal vascular lesions of underperfusion in the placenta. Our findings imply that the variant identified in the ADAMTS13 gene in our cohort may have a specific functional impact on the placenta, and that treatment with fresh frozen plasma during pregnancy ameliorates the course of the disease, leading to a milder phenotype or a normal pregnancy in the majority of cases.

Changes in trends over time for the specific contribution of different risk factors for pre-eclampsia.

PURPOSE: The prevalence of risk factors for pre-eclampsia has changed over time; however, little is known regarding how these changes have altered the specific contribution of each risk factor. We aim to identify trends in the contribution of different risk factors throughout different time intervals. METHODS: We compared the prevalence and odds-ratio of different known risk factors for pre-eclampsia occurring in three equal population groups from 1988 to 2014. Data was retrieved from our medical center's perinatal database. A multivariable logistic regression model was employed to identify independent risk factors for pre-eclampsia. We evaluated changes in risk factors and their specific contribution to the occurrence of pre-eclampsia over time and a comparison of the prevalence and odds-ratios of chosen risk factors between the three time periods was performed. RESULTS: 295,946 pregnancies met the inclusion criteria; of those, 16,246 (5.5%) were complicated with pre-eclampsia with the incidence increasing from 8 to 11%. Chronic hypertension, systemic lupus erythematosus, pre-gestational diabetes mellitus, twin pregnancy, advanced maternal age and fertility treatments were found to be the strongest independent risk factors. While rates of twin pregnancies and pre-gestational diabetes mellitus have demonstrated a linear increase, fertility treatments demonstrated a linear decrease. Chronic hypertension and systemic lupus erythematosus resulted in a mixed trend. CONCLUSION: In our study, not only did the rates of different risk factors for pre-eclampsia change over the study period, the specific contribution of each risk factor for the occurrence of pre-eclampsia changed as well. Developing a better understanding of these trends might aid in our ability to predict this major complication and to improve maternal and fetal outcomes.

Risk factors for early postpartum hemorrhage: A retrospective, population-based, cohort analysis.

OBJECTIVE: To identify risk factors for developing early postpartum hemorrhage (PPH) and to examine whether risk factors vary according to severity and mode of delivery. METHODS: A population-based cohort study was conducted in which all deliveries at a tertiary medical center were included. Risk factors for developing early PPH were compared based on the severity of bleeding as well as the mode of delivery. Multiple logistic regression models were used to control for confounders. RESULTS: Among 322 497 deliveries included in the analysis, early PPH complicated 1811 (0.56%) of all deliveries. Among all cases of early PPH, 505 deliveries (28%) were complicated with severe PPH. Using a logistic regression model, in vitro fertilization (IVF) pregnancy, previous cesarean delivery (CD), pre-eclampsia, placental abruption, and uterine rupture were independently associated only with severe early PPH, while non-progressive second stage of labor, induction of labor, and large for gestational age were independently associated with both severe and mild early PPH. When applying an additional logistic regression model, whereas IVF pregnancy, pre-eclampsia, and large for gestational age were independently associated with early PPH among vaginal deliveries only, placenta previa was independently associated with early PPH among CD only. CONCLUSIONS: Independent risk factors for developing severe PPH solely include IVF pregnancy, previous CD, pre-eclampsia, placental abruption, and uterine rupture. IVF pregnancy, pre-eclampsia, and large for gestational age are independent risk factors for early PPH following vaginal delivery, while placenta previa is independently associated with early PPH after CD only. Due to the recognition of the importance of both the provider and institutional planning and preparation for PPH, the study's results should be viewed within the scope of its retrospective cohort design.

Fetal Growth Restriction and Long-Term Cardiovascular Morbidity of Offspring in Dichorionic-Diamniotic Twin Pregnancies.

Objective: We opted to investigate whether fetal growth restriction (FGR) in dichorionic-diamniotic twins is a risk factor for long-term cardiovascular morbidity in offspring. Study design: A population-based retrospective cohort study, comparing long-term cardiovascular morbidity among FGR and non-FGR twins, born between the years 1991 and 2021 in a tertiary medical center. Study groups were followed until 18 years of age (6570 days) for cardiovascular-related morbidity. A Kaplan-Meier survival curve compared the cumulative cardiovascular morbidity. A Cox proportional hazard model assisted with adjusting for confounders. Results: In this study, 4222 dichorionic-diamniotic twins were included; 116 were complicated with FGR and demonstrated a significantly higher rate of long-term cardiovascular morbidity (4.4% vs. 1.3%, OR = 3.4, 95% CI 1.35-8.78, p = 0.006). The cumulative incidence of long-term cardiovascular morbidity was significantly higher among FGR twins (Kaplan-Meier Log rank test p = 0.007). A Cox proportional-hazard model found an independent association between FGR and long-term cardiovascular morbidity, when adjusted for both birth order and gender (adjusted HR 3.3, 95% CI 1.31-8.19, p = 0.011). Conclusions: FGR in dichorionic-diamniotic twins is independently associated with an increased risk for long-term cardiovascular morbidity in offspring. Therefore, increased surveillance may be beneficial.

von Willebrand factor antigen: a biomarker for severe pregnancy complications in women with hereditary thrombotic thrombocytopenic purpura?

BACKGROUND: Hereditary thrombotic thrombocytopenic purpura (hTTP) is associated with severe obstetric morbidity (SOM) during pregnancy. Treatment with fresh frozen plasma (FFP) mitigates the risk in some women, but others respond poorly and continue to suffer obstetric complications. OBJECTIVES: To determine a possible association between SOM and elevated nonpregnant von Willebrand factor (NPVWF) antigen levels in women with hTTP and whether the latter can predict the response to FFP transfusion. METHODS: This was a cohort-based study of women with hTTP due to homozygous c.3772delA mutation of ADAMTS-13 who had pregnancies both with and without FFP treatment. Occurrences of SOM were determined from medical records. Generalized estimated equation logistic regressions and receiver operating characteristic curve analysis determined the NPVWF antigen levels associated with the development of SOM. RESULTS: Fourteen women with hTTP had 71 pregnancies; of which 17 (24%) culminated in pregnancy loss and 32 (45%) were complicated by SOM. FFP transfusions were administered in 32 (45%) of the pregnancies. Treated women had decreased SOM (28% vs 72%, p < .001) and preterm thrombotic thrombocytopenic purpura exacerbations (18% vs 82%, p < .001) and higher median NPVWF antigen levels than those of women with uncomplicated pregnancies (p = .018). Among the treated women, median NPVWF antigen levels were higher in those with SOM than in those without SOM (225% vs 165%, p = .047). Logistic regression models demonstrated a significant 2-way association between elevated NPVWF antigen levels (for SOM, odds ratio, 1.08; 95% CI, 1.001-1.165; p = .046) and SOM (for elevated NPVWF antigen levels, odds ratio, 1.6; 95% CI, 1.329-1.925; p < .001). The receiver operating characteristic curve analysis demonstrated that an NPVWF antigen level of 195% had 75% sensitivity and 72% specificity for SOM. CONCLUSION: Elevated NPVWF antigen levels are associated with SOM in women with hTTP. Women with levels >195% may benefit from increased surveillance and more intensive FFP treatment during pregnancy.

Maternal Systemic Lupus Erythematosus (SLE) High Risk for Preterm Delivery and Not for Long-Term Neurological Morbidity of the Offspring.

OBJECTIVE: Pregnancies of women with systemic lupus erythematosus (SLE) are associated with preterm delivery. As preterm delivery is associated with long-term neurological morbidity, we opted to evaluate the long-term neurologic outcomes of offspring born to mothers with SLE regardless of gestational age. METHODS: Perinatal outcomes and long-term neurological disease of children of women with and without SLE during pregnancy were evaluated. Children of women with and without SLE were followed until 18 years of age for neurological diseases. Generalized estimating equation (GEE) models were used to assess perinatal outcomes. To compare cumulative neurological morbidity incidence a Kaplan-Meier survival curve was used, and a Cox proportional hazards model was used to control for confounders. RESULT: A total of 243,682 deliveries were included, of which 100 (0.041%) were of women with SLE. Using a GEE model, maternal SLE was noted as an independent risk factor for preterm delivery. The cumulative incidence of long-term neurological disease was not found to be significantly higher when using the Kaplan Meier survival curves and maternal SLE was not found to be associated with long-term neurological disease of the offspring when a Cox model was used. CONCLUSION: Despite the association of SLE with preterm delivery, no difference in long-term neurological disease was found among children of women with or without SLE.

Identifying the Critical Threshold for Long-Term Pediatric Neurological Hospitalizations of the Offspring in Preterm Delivery.

We opted to investigate whether a critical threshold exists for long-term pediatric neurological morbidity, and cerebral palsy (CP), in preterm delivery, via a population-based cohort analysis. Four study groups were classified according to their gestational age at birth: 24-27.6, 28-31.6, 32-36.6 weeks and term deliveries, evaluating the incidence of long-term hospitalizations of the offspring due to neurological morbidity. Cox proportional hazard models were performed to control for confounders. A Kaplan-Meier survival curve was used to compare the cumulative neurological morbidity incidence for each group. A total of 220,563 deliveries were included: 0.1% (118) occurred at 24-27.6 weeks of gestation, 0.4% (776) occurred at 28-31.6 weeks of gestation, 6% (13,308) occurred at 32-36.6 weeks of gestation and 93% (206,361) at term. In a Cox model, while adjusting for confounders, delivery before 25 weeks had a 3.9-fold risk for long-term neurological morbidity (adjusted HR (hazard ratio) = 3.9, 95% CI (confidence interval) 2.3-6.6; p < 0.001). The Kaplan-Meier survival curve demonstrated a linear association between long-term neurological morbidity and decreasing gestational age. In a second Cox model, adjusted for confounders, infants born before 25 weeks of gestation had increased rates of CP (adjusted HR = 62.495% CI 25.6-152.4; p < 0.001). In our population, the critical cut-off for long-term neurological complications is delivery before 25 weeks gestation.