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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., (© 2023 Wiley Periodicals LLC.)

Purpose: Pruritus during pregnancy is associated with adverse maternal, pregnancy, and neonatal outcomes. We opted to assess the association between term pruritus and long-term neuropsychiatric hospitalizations of the offspring., Methods: In a population-based retrospective cohort study, the incidence of long-term neuropsychiatric hospitalizations was compared between offspring born to women with or without pruritus at term. Neuropsychiatric morbidity was assessed up to the age of 18 years according to ICD-9 codes associated with hospitalization of the offspring. A Kaplan-Meier survival curve was used to compare cumulative neuropsychiatric hospitalizations incidence and Cox proportional hazards models were used to control for confounders. The study included 226,918 deliveries of which 600 (0.26%) were in women with term pruritus., Results: Offspring born to women with pruritus exhibited a higher rate of long-term neuropsychiatric hospitalizations, specifically due to developmental and neurodegenerative disorders. Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of long-term neuropsychiatric hospitalizations in offspring of women with pruritus. Using several Cox proportional hazards models, being born to a woman with pruritus was independently associated with an increased risk of long-term neuropsychiatric hospitalizations., Conclusions: Maternal term pruritus was found to be independently associated with long-term neuropsychiatric hospitalizations of the offspring., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In this study we sought to ascertain a critical threshold of the degree of prematurity and long-term digestive morbidity of the offspring., Methods: A population-based cohort analysis was conducted, comparing long-term incidence of digestive morbidity in infants born preterm. Cases were divided into four groups according to the extremity of prematurity. Digestive morbidity included hospitalizations involving a predefined set of ICD9 codes. A Kaplan-Meier survival curve was constructed to compare cumulative incidence of digestive morbidity. A Cox proportional hazards model was used to control for confounders., Results: During the study period 220,563 patients met the inclusion criteria. Offspring born preterm had significantly more hospitalizations due to digestive morbidity compared to term offspring. The Kaplan-Meier survival curve demonstrated significant higher cumulative incidence of long-term digestive morbidity of the offspring with decreasing gestational age (Log rank p < 0.001). The risk was highest at 28 weeks gestation. Using a Cox proportional hazards model, being born at very and moderate to late preterm birth was independently associated with long-term digestive morbidity., Conclusion: Preterm delivery is an independent risk factor for long-term digestive morbidity of the offspring. In our population, 28 weeks gestation is the critical cut-off for pronounced digestive morbidity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Problem: Drug allergies are increasingly common. Immunological factors, implicated in many neurological diseases, also influence an individual's susceptibility. We sought to ascertain a possible association between maternal drug allergy and long-term neurological-related hospitalizations in the offspring., Method of Study: This is a population-based cohort analysis, comparing the long-term risk of neurological-related hospitalization, involving a predefined set of ICD9 codes as recorded in hospital records, of children born to mothers with and without drug allergies. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Twin pregnancies, fetal malformations, and cases of perinatal mortality were excluded. A Kaplan-Meier survival curve was constructed to compare cumulative neurological hospitalizations. A Cox proportional hazards model was used to control for time to event., Results: The study included 242 342 patients, 9714 with known drug allergy (4%). Offspring born to mothers with drug allergies had significantly more neurological hospitalizations compared to controls (4.2% vs 3.1%; P ≤ .001; Kaplan-Meier log-rank test P ≤ .001), specifically for psychiatric disorders including eating disorders (0.3% vs 0.2%;P = .002), attention-deficit/hyperactivity disorder (0.124% vs 0.056%; P = .008), emotional disorders (0.8% vs 0.5%; P ≤ .001), and movement disorders (2.3% vs 1.8%; P = .002). While controlling for birth year, gestational age, maternal age, maternal diabetes, hypertensive disorders, and cesarean delivery, using a Cox proportional hazards model, maternal drug allergy was found to be an independent risk factor for neurological hospitalization of the offspring (adjusted HR 1.3, 95% CI 1.19-1.45 P < .001)., Conclusion: Being born to a mother with known drug allergy is an independent risk factor for long-term neurological hospitalization of the offspring., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pregnancy with an Intrauterine device (IUD) is a risk factor for adverse pregnancy outcomes. The purpose of this study was to examine a possible association between presence of IUD during pregnancy and long-term incidence of infectious-related hospitalizations of the offspring., Methods: A population-based cohort analysis was performed including all singleton deliveries between 1991 and 2014 at a single tertiary hospital. Primary exposure was defined as delivery of an infant to a mother who conceived with an IUD, that was either removed or retained during pregnancy. Offspring of mothers who conceived without an IUD comprised the comparison group. The main outcome evaluated was infectious-related hospitalizations of the offspring up to the age of 18 years., Results: The number of deliveries that met the inclusion criteria was 227,431, of which 209 were to mothers who conceived with an IUD that was removed and 52 were to mothers who retained their device. Long-term incidence of infections-related hospitalizations was compared between the groups (12.5% in the retained IUD, 12.9% in the removed IUD and 11.2% in the No-IUD group, P = 0.638). A Kaplan-Meier survival curve did not demonstrate a significantly higher cumulative incidence of infectious-related hospitalizations in offspring of women who conceived with an IUD (log-rank P = 0.340). In a Cox regression model, while controlling for confounders such as maternal age and preterm birth, conceiving with an IUD was not found to be independently associated with long-term incidence of infectious-related hospitalizations of the offspring., Conclusion: Offspring of women conceiving with an IUD are not at increased risk for long-term incidence of infectious-related hospitalizations.

Objective: Gestational diabetes mellitus (GDM) was previously found to be an independent risk factor for long-term cardiovascular morbidity of parturients and their offspring. The objective of this study was to investigate the association between family history of diabetes mellitus (DM) in non-diabetic mothers and long-term pediatric cardiovascular hospitalizations of their offspring., Study Design: In a hospital-based cohort study, the incidence of cardiovascular disorders was compared between offspring of non-diabetic mothers with and without a family history of DM. Cardiovascular hospitalizations were assessed up until 18years of age according to a predefined set of ICD-9 codes associated with hospitalization of offspring. Exclusion criteria included multiple gestations, mothers with pre-gestational or gestational diabetes, lack of prenatal care, and children with congenital malformations and chromosomal abnormalities. A Kaplan-Meier survival curve was used to compare cumulative hospitalizations incidence. A cox proportional hazards model was performed to control for confounders., Results: A total of 208,728 deliveries were included in the study. Of them, 17,040 (8.2%) offspring were born to non-diabetic mothers with a family history of DM. Significant differences in the rates of IVF, induction of labor, obesity, hypertensive disorders of pregnancy, smoking and birth weight were found between the two study groups. Total cardiovascular hospitalizations were comparable between the study groups (0.6% vs. 0.7%, p=0.416). The Kaplan-Meier survival curve exhibited no difference in the cumulative incidence of total cardiovascular hospitalizations of the offspring (log-rank test, p=0.271). A Cox regression model found that a family history of DM in non-diabetic mothers was not independently associated with long-term cardiovascular hospitalizations of the offspring after controlling for the following confounders: maternal age, birth weight, caesarian section and maternal hypertensive disorders (aHR=1.130, 95% CI 0.930-1.374, p=0.220)., Conclusion: A family history of DM in non-diabetic parturients, does not increase the risk for cardiovascular hospitalizations of their offspring., (Copyright © 2019 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate short-term adverse perinatal outcomes and long-term neuropsychiatric hospitalizations through 18 years of age in offspring conceived during copper intrauterine device (IUD) use., Study Design: We conducted a population-based cohort study comparing the pregnancy outcomes after 22 weeks of women who conceived with a copper IUD that was removed, women with a retained IUD and pregnancies without an IUD. Deliveries occurred between the years 1991 and 2014. We used a multivariable generalized estimating equation (GEE) logistic regression model analysis to control for confounders and for maternal clusters, a Kaplan-Meier survival curve to compare cumulative neuropsychiatric hospitalizations incidence and a Cox proportional-hazards model to evaluate long-term neuropsychiatric hospitalizations., Results: During the study period there were 221,805 deliveries, of which 203 (0.09%) and 149 (0.06%) occurred in patients with removed or retained copper IUD, respectively. Using GEE models, preterm delivery was independently associated with copper IUD use [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.4-3.2 and OR 2.3, 95% CI 1.4-3.7 for removed and retained IUD, respectively]. We did not find an association between copper IUD presence or removal and the offspring's long-term neuropsychiatric hospitalizations (total long-term neuropsychiatric hospitalizations: 2.5%, 4.4% and 3.2% for removed, retained and no IUD, respectively, p=.71). Long-term neuropsychiatric hospitalization rate was comparable between the groups (Kaplan-Meier survival curve log rank p=.23)., Conclusion: Pregnancies in women who conceive with a removed or retained copper IUD are at an increased risk for short-term adverse perinatal outcomes, especially preterm delivery. For pregnancies that continued to at least 22 weeks, we found no benefit in IUD removal. However, the risk of long-term neuropsychiatric hospitalizations is not increased among offspring of these women., Implications: Our data are insufficient to make a recommendation as to whether removal or retention of a copper IUD during pregnancy is best, as after 22 weeks' gestation we have found no benefit in IUD removal. Careful surveillance and categorization of the pregnancy as "high risk" are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To assess whether delivery of small for gestational age (SGA) neonates to mothers with gestational diabetes mellitus (GDM) increases the risk of long-term cardiovascular offspring hospitalizations compared to SGA neonates born to mothers without GDM., Study Design: This is a population-based retrospective cohort study. The study group was SGA offspring born to mothers with GDM (n = 259), while the control group was SGA offspring born to mothers without GDM (n = 9053). The main factor evaluated was offspring cardiovascular hospitalizations up to the age of 18 years. Kaplan-Meier survival curve was used to estimate cumulative incidence of cardiovascular hospitalizations. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (HR) for cardiovascular hospitalizations., Results: SGA children born to mothers with GDM had significantly higher rates of cardiovascular-related hospitalizations (1.9% vs. 0.7%, p = .026). A Kaplan-Meier survival curve demonstrated that SGA children born to GDM mothers had a higher cumulative incidence of cardiovascular hospitalizations (log-rank p = .037). The Cox regression model, while controlling for confounders, demonstrated that delivery of SGA neonates to mothers with GDM is independently associated with long-term cardiovascular offspring hospitalizations (adjusted HR =2.6; 95% CI 1.02-6.55 p = .045)., Conclusion: Delivery of SGA neonates born to mothers with GDM is independently associated with long-term cardiovascular offspring hospitalizations.

Background: Placental abruption is a major determinant of maternal and perinatal morbidity and mortality, often related to asphyxia and preterm birth. However, the impact of abruption on the long-term morbidity of the offspring is less investigated., Methods: We designed a hospital-based cohort study, in which the incidence of long-term neurology-related hospitalisations of offspring to women with and without placental abruption was assessed. All singleton deliveries between 1991 and 2014 were included in the study. Congenital anomalies, perinatal mortality, and multifetal pregnancies were excluded from the analyses. We compared cumulative morbidity incidence using Kaplan-Meier survival curves and estimated the risk for long-term neurological hospitalisations from Cox proportional hazards models after adjustment for putative including maternal age, parity, hypertensive disorders, pre-gestational and gestational diabetes, gender, ethnicity, and year of birth., Results: Over the 22-year period, 2 202 269 person-years of follow-up, there were 217 910 deliveries of which 0.5% (n = 1003) were complicated with placental abruption. The median (interquartile range) follow-up of children in the abruption and non-abruption groups was 10.3 (4.6, 15.9) and 12.0 (6.3, 16.5) years, respectively. The cumulative incidence of total neurological hospitalisations was comparable between abruption (3.32 per 1000 person-years) and non-abruption (3.16 per 1000 person-years). Abruption was associated with increased rates of cerebral palsy (hazard ratio [HR] 6.71, 95% CI 3.32, 13.58) and developmental disorders (HR 3.36, 95% CI 1.38, 8.13), but not for total neurology-related hospitalisations (HR 1.08, 95% CI 0.78, 1.49)., Conclusion: Placental abruption is associated with increased rate of cerebral palsy and developmental disorders in the offspring later in life. This study may define risk factors for childhood neuropsychiatric disorders, enabling early diagnosis and intervention in children with such disorders, and perhaps improving their prognosis., (© 2019 John Wiley & Sons Ltd.)

Objective: We aimed to evaluate the association between advanced maternal age and the long-term health of the offspring., Methods: In this population-based cohort study, hospitalizations of offspring up to the age of 18 years were compared according to maternal age. The incidence of long-term hospitalizations of the offspring due to cardiovascular, endocrine, neurological, hematological, respiratory and gastro-intestinal morbidities was evaluated. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence. Cox regression models were performed to control for confounders., Results: During the study period, 202,709 deliveries were included, of which 26,287 (12.9%) were in women aged 35-39 years, and 6,718 (3.3%) in women aged 40-50 years. Children born to older mothers did not have a significantly different cumulative incidence of long-term pediatric morbidities evaluated, as compared with the comparison group, using Kaplan-Meier survival analyses. In the Cox regression analyses, advanced maternal age did not exhibit an independent association with long-term morbidities of the offspring., Conclusion: Despite the association of advanced maternal age with adverse maternal and immediate neonatal outcomes, there does not seem to be an association with the long-term morbidity of the offspring., (© 2018 S. Karger AG, Basel.)

Objective: To investigate whether obesity during pregnancy poses a risk for subsequent maternal long-term cardiovascular morbidity, after controlling for diabetes and hypertensive disorders., Study Design: Data were analyzed from consecutive pregnant women who delivered between 1988 and 1999, and were followed-up until 2010. Long-term cardiovascular morbidity was compared among women with and without obesity in pregnancy (maternal pre-pregnancy body mass index (BMI) of 30 kg/m(2) or more). Kaplan-Meier survival curves were used to compare cumulative incidence of cardiovascular hospitalizations. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for long-term cardiovascular hospitalizations., Results: During the study period 46 688 women met the inclusion criteria, 1221 (2.6%) had a BMI ≥30 kg/m(2). During a follow-up period of more than 10 years, patients with obesity had higher rates of simple cardiovascular events and total number of cardiovascular hospitalizations. These complications tended to occur at a shorter interval (mean 4871 days ± 950 versus 5060 days ± 1140; p = 0.001). In a Cox proportional hazards model that adjusted for diabetes mellitus, preeclampsia and maternal age, obesity was independently associated with cardiovascular hospitalizations (adjusted HR 2.6, 95% CI 2.0-3.4)., Conclusion: Obesity during pregnancy is an independent risk factor for long-term cardiovascular morbidity, and these complications tend to occur earlier. Pregnancy should be considered as a window of opportunity to predict future health problems and as an opportunity to promote women's health. Obese parturients might benefit from cardiovascular risk screening that could lead to early detection and secondary prevention of cardiovascular morbidity.