Prenatal Exposure to Acid Suppressor Medications and Development of Ductus Arteriosus in Term Newborns.

OBJECTIVE: The ductus arteriosus normally closes after birth. Histamine 2 receptor antagonist (H2RA) has been associated with patent ductus arteriosus (PDA). We aimed to study the characteristics of term infants with PDA and their possible association with prenatal exposure to antacids-proton pump inhibitors (PPIs) and H2RA. STUDY DESIGN: This was a population-based matched case-control study of mothers registered at "Clalit" Health Maintenance Organization (HMO) and their infants born at "Soroka" University Medical Center (SUMC) between 2001 and 2018. Cases are defined as term infants born with PDA diagnosed by echocardiography and registered in the postdelivery discharge form. Each case was matched with four term newborns without PDA diagnosis. Exposure window was defined by the timing of first purchase of H2RA or PPI during pregnancy and based on information from a computerized medication database (Clalit HMO, SUMC). RESULTS: PDA was diagnosed in 1,884 term infants (4.9%). Characteristics included a significantly higher percentage of lack of prenatal care, cesarean section, in vitro fertilization, polyhydramnios, oligohydramnios, Apgar 1 minute <5, and prenatal exposure to H2RA (odds ratio [OR] 4.18) and PPIs (OR 3.50; all p < 0.001). PDA association with exposure window was similar in each trimester (1.5-2%) for both H2RA and PPI. CONCLUSION: PDA incidence in term infants in our population was greater than previously reported. PPI and H2RA are both antiacids with different mechanisms of action. The similar OR for exposure to one as well as the other, and the lack of influence of the initial exposure period, are compatible with bias. KEY POINTS: · Term newborns with PDA have different characteristics than newborns without PDA.. · Prenatal exposure to PPIs or H2RA is associated with greater risk of PDA in term newborns.. · The possible effect mechanism of PPIs on the ductus is unclear and understudied..

Cesarean versus vaginal delivery for breech presentation is an independent risk factor for long-term pediatric respiratory hospitalization of the offspring.

OBJECTIVES: To compare the long-term respiratory morbidity of offspring born by cesarean delivery for breech presentation with that of those delivered vaginally. METHODS: A population-based cohort analysis including all singleton breech deliveries between the years 1991 and 2014, comparing long-term respiratory morbidity of offspring born in breech presentation, according to mode of delivery. Offspring with congenital malformations, perinatal deaths, and instrumental deliveries were excluded. Respiratory morbidity included hospitalizations (up to age 18 years), as recorded in hospital records. A Kaplan-Meier survival curve compared cumulative respiratory morbidity. A Weibull parametric survival model controlled for confounders and repeat deliveries. RESULTS: A total of 7337 breech deliveries were included; 6376 (86.9%) cesarean deliveries and 961 (13.1%) vaginal breech deliveries. The Kaplan-Meier survival curve demonstrated higher cumulative incidence of respiratory morbidity in the cesarean delivery group compared with vaginal delivery (log rank test P = 0.006). Using a Weibull parametric survival model to control for confounders, cesarean delivery was found to be an independent risk factor for long-term respiratory morbidity of the offspring (adjusted hazard ratio 1.87, 95% confidence interval 1.32-2.65, P < 0.001). CONCLUSIONS: Cesarean versus vaginal delivery for breech presentation is an independent risk factor for long-term pediatric respiratory morbidity of the offspring.

Elective cesarean delivery and long-term cardiovascular morbidity in the offspring - a population-based cohort analysis.

OBJECTIVE: To evaluate the impact of cesarean delivery (CD) on offspring risk for long-term cardiovascular morbidity. STUDY DESIGN: A population-based cohort analysis was performed, including all singleton term deliveries occurring between 1991 and 2014 at a single tertiary medical center. A comparison was performed between children delivered via CD and those delivered vaginally. Fetuses with cardiac or other congenital malformations were excluded, as were cases of urgent CD and pregnancies involving preeclampsia, gestational diabetes, placenta previa, labor induction, fetal growth restriction, preterm PROM, and instrumental deliveries. Hospitalizations of the offspring up to 18 years of age involving cardiovascular morbidity were compared between the two study groups. A Kaplan-Meier survival curve compared cumulative cardiovascular morbidity incidence and a Cox regression model controlled for confounders. RESULTS: Of the 132,054 term deliveries who met the inclusion criteria; 8.9% were CDs (n = 11,746) and 91.1% (n = 120,308) were vaginal deliveries. Cardiovascular hospitalization incidence per 1000 person follow up years was 0.742 in the CD group and 0.054 in the comparison group (HR = 1.3, 95%CI 1.051-1.710, p = .018). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of cardiovascular morbidity following CD (log rank p = .018). In the Cox proportional hazards model, CD was noted as an independent risk factor for offspring long-term pediatric cardiovascular morbidity (adjusted HR = 1.295, CI 1.005-1.668, p = .04) when controlling for maternal age, obesity, ethnicity, gestational age, newborn gender, low birthweight, maternal preexisting cardiovascular disease, and deliveries occurring after 2008. CONCLUSION: Singletons delivered by CD at term have an increased risk of long-term cardiovascular morbidity.

Association Between Mode of Delivery of the Breech Fetus and Hospitalizations Due to Inflammatory Bowel Disease During Childhood.

BACKGROUND AND GOALS: While evidence suggests short-term benefits in neonatal morbidity and mortality from cesarean delivery of the fetus in breech presentation, the long-term implications for the offspring are less clear. To assess the implications of the mode of delivery on offspring's health, we have evaluated the long-term gastrointestinal (GI) morbidity of offspring with a breech presentation delivered in either way. MATERIALS AND METHODS: A population-based retrospective cohort study including singleton deliveries in breech presentation occurring between 1991 and 2014 at a tertiary referral hospital. Incidence of hospitalizations of the offspring up to the age of 18 years involving GI morbidity was compared between those delivered via cesarean section or vaginally. A Kaplan-Meier survival curve compared cumulative GI morbidity. A Weibull parametric survival model controlled for confounders while accounting for repeated occurrence of mothers and dependence among siblings. RESULTS: Overall, 86.9% (n=6376) of the 7337 fetuses in breech presentation, were delivered abdominally. Hospitalizations involving GI morbidity were higher in offspring delivered by cesarean section, specifically due to inflammatory bowel disease (IBD). Kaplan-Meier survival curve revealed the higher cumulative incidence of total GI morbidity and IBD specifically in the cesarean delivery group (P<0.001 and P=0.004, respectively). Using a Weibull parametric while controlling for relevant confounders, cesarean delivery emerged as an independent risk factor for long-term IBD-related morbidity of the offspring delivered in breech presentation (adjusted hazard ratio=3.18, 95% confidence interval: 1.47-6.87, P=0.003). CONCLUSION: Cesarean delivery is associated with higher rates of hospitalizations due to IBD and total GI morbidity during childhood in term singleton in breech presentation.

Exposure to metals and morbidity at eight years follow-up in women of childbearing age.

This exploratory study was aimed to investigate the link between toxic metal content in women's urine and their morbidity 2 years before and 6 years after the test. Concentrations of 25 metals in urine were analyzed for 111 pregnant women collected prior to delivery. All women were of Arab-Bedouin origin. Information on primary care and hospital visits during the study period was obtained. In a Poisson regression model, a health outcome was regressed over metal exposure and other factors. A Weighted Quantile Sum Regression (WQS) approach was used to indicate metals dominating in their possible impact on women's morbidity. Obesity was the most frequently diagnosed condition in this population (27.9%). Diagnoses in a neurological category accounted for 36.0%, asthma or respiratory-25.2%, psychiatric-12.6%, cardiovascular-14.4% and cancer or benign growth-for 13.5%. Based on WQS analysis, cancer and benign growth were mostly attributed to the increased levels of cadmium, cardiovascular outcomes were linked with lead, and obesity was found associated with elevated levels of nickel. Hematological, neurological and respiratory outcomes were attributed to multiple non-essential metals. The health and exposure profile of women in the study warrants a periodic biomonitoring in attempt to identify and reduce exposure to potentially dangerous elements.

Meconium stained amniotic fluid exposure and long-term respiratory morbidity in the offspring.

OBJECTIVE: Meconium stained amniotic fluid (MSAF) is a well-established risk factor for neonatal short-term respiratory complications. Little is known regarding the long-term morbidity. We investigated the possible association between MSAF and offspring respiratory morbidity. METHODS: A population-based, cohort study of singleton deliveries occurring between 1991 and 2014 at a sole regional tertiary medical center was performed. Incidence of offspring respiratory related hospitalizations up to the age of 18 years were evaluated and compared to unexposed offspring. A Kaplan-Meier survival curve was used to compare cumulative respiratory morbidity incidence, and a Cox proportional hazards model was used to control for confounders. RESULTS: During the study period 242,342 deliveries met the inclusion criteria. Of them, 14.7% (n = 35,609) were complicated with MSAF. Incidence of respiratory-related hospitalizations was significantly lower in children exposed to MSAF as compared to the unexposed group (4.5% vs. 4.9%, respectively; p < .01). Specifically, hospitalizations involving pneumonitis were significantly less common among the MSAF group (odds ratio, 0.35; 95% confidence interval [95% CI], 0.13-0.96; p = .03). The Kaplan-Meier survival curve demonstrated significantly lower total cumulative respiratory morbidity rates in the MSAF exposed group (log rank p < .01). In the Cox model, controlled for clinically relevant confounders, MSAF exhibited an independent and significant protective effect on long-term childhood respiratory morbidity (aHR, 0.91; 95% CI, 0.86-0.96; p < .01). CONCLUSIONS: Fetal exposure to MSAF during labor appears to be associated with lower rates of long-term respiratory related hospitalizations in the offspring. Changes in offspring microbiome, as well as functional and anatomical modulations possibly resulting from MSAF exposure, might offer a plausible explanation of our findings.

Maternal metal concentration during gestation and pediatric morbidity in children: an exploratory analysis.

BACKGROUND: The majority of studies linking exposure to metals with certain health outcomes focus on known toxic metals. Alternatively, this study assesses the extent to which exposure to a wider range of metals during gestation is associated with childhood morbidity. METHODS: We analyzed the concentrations of 25 metals found in urine samples of 111 pregnant women of Arab-Bedouin origin collected prior to birth. In addition, we collected medical records on their offspring for six years following birth, including every interaction with HMOs, local hospitals, and pharmacies. RESULTS: The main types of morbidities diagnosed and treated during this period were preterm births, malformations, asthma-like morbidity, cardiovascular and behavioral problems, and obesity. Multivariable analysis showed that offspring born before term were more likely to have been exposed to elevated maternal concentrations of zinc, thallium, aluminum, manganese, and uranium, all with adjusted relative risk above 1.40 for an increase by each quintile. Likewise, children with asthma had been exposed to higher levels of magnesium, strontium, and barium at gestation, while behavioral outcomes were associated with elevated biometals, i.e., sodium, magnesium, calcium, selenium, and zinc, as well as higher levels of lithium, cobalt, nickel, strontium, cadmium, vanadium, arsenic, and molybdenum. A heatmap of adjusted relative risk estimates indicates the considerable implications that exposure to metals may have for preterm birth and developmental outcomes. CONCLUSIONS: The current study shows that perinatal exposure to metals is adversely associated with pediatric morbidity. Further such analyses on additional samples are warranted.

Isolated Single Umbilical Artery as a Risk Factor for Urinary Tract Infections in Childhood.

OBJECTIVE: This study aimed to determine whether isolated single umbilical artery (iSUA), even absent identifiable genitourinary (GU) abnormalities, increases the risk of GU infection during childhood. STUDY DESIGN: Retrospective population-based comparison of fetuses with iSUA versus normal three-vessel cords. Fetuses with growth restriction, prematurity, multiple gestations, and anatomical or chromosomal anomalies were excluded. The primary outcome was hospital-associated GU infection during the first 18 years of life. Kaplan-Meier's survival curves were used to assess cumulative risk; Cox's multivariable models were used to adjust for confounders. RESULTS: Among 227,599 term singleton deliveries, children with iSUA (n = 729) had a higher incidence (1.8 vs. 0.6%, p < 0.001) and cumulative incidence (log-rank test, p < 0.001) of hospital-associated GU infection. The Cox's models confirmed these findings (hazard ratio: >2.82, confidence interval: 1.63-4.87 in composite models). CONCLUSION: iSUA represents an independent risk factor for GU infection. Urinary tract imaging may be warranted.

Optimal delivery timing for dizygotic twins - the short- and long-term perspective.

Major obstetrics and gynecology societies offer inconsistent recommendation regarding optimal delivery timing in uncomplicated dizygotic twins. We sought to investigate the impact of delivery timing within term gestation, in dizygotic twins, on the short- and long-term offspring morbidity. A prospectively analyzed cohort of dizygotic twin deliveries was conducted. All women delivered at a regional tertiary medical center, at term (≥37 0/7), between the years 1991 and 2014, were included. The primary exposure was delivery at 37 0/7-37 + 6/7 weeks, while delivery at ≥38 0/7 weeks' gestation was considered the reference. Neonatal short- and long-term outcomes according to hospitalizations of offspring up to 18 years of age due to cardiac, respiratory, hematological, neurological, and infectious morbidity were compared. Kaplan-Meier survival curves were used to compare cumulative incidences per each major-system hospitalization. Cox regression models were used to estimate the adjusted hazard ratios, while adjusting for variables with clinical importance. During the study period, 612 dizygotic twin deliveries met the inclusion criteria. Of them, 200 (31.3%) occurred at 37-37 6/7 weeks, and 412 (68.7%) occurred at ≥38 0/7 weeks' gestation. In the long-term analysis, rates of hospitalizations involving several major morbidity categories exhibited comparable rates in both groups. The Cox regression models did not demonstrate an independent association between gestational age within term and later major pediatric morbidity in offspring (total long-term morbidity: adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.29). Dizygotic twin deliveries occurring at different gestational ages within term do not appear to significantly impact on major short- and long-term outcomes.

Prenatal exposure to isolated amniotic fluid disorders and the risk for long-term endocrine morbidity of the offspring.

BACKGROUND: Amniotic fluid abnormalities may be associated with adverse perinatal outcomes, some of which are endocrine related. OBJECTIVE: To evaluate whether in utero exposure to amniotic fluid abnormalities is associated with long-term endocrine morbidity in the offspring. STUDY DESIGN: In this cohort study, the incidence of long-term endocrine disorders was compared between singletons exposed and non-exposed to oligohydramnios or polyhydramnios. RESULTS: During the study period, 195 943 newborns were included in the study, of them 2.0% (n = 4072) and 2.9% (n = 5684) were exposed to oligohydramnios and polyhydramnios, respectively. Long-term endocrine morbidity was higher among children exposed to isolated amniotic fluid disorders, as was also noted in the Kaplan-Meier survival curve (log-rank test p < 0.001). Abnormal amniotic fluid volume was found to be independently associated with long-term endocrine morbidity of the offspring according to a Cox regression model controlled for clinically related confounders. CONCLUSION: In utero exposure to isolated amniotic fluid abnormalities is independently associated with long-term endocrine morbidity in the offspring.

Targeted and universal screen in term and preterm infants for congenital CMV infection.

Background: The aims of this study were to evaluate the incidence of congenital cytomegalovirus (CMV) in term and near-term infants who fail hearing screen (target screening), the incidence of congenital CMV infections in infants born before 33 weeks of gestation (universal screening) and the incidence of infants who need pharmacologic treatment for congenital CMV associated sensorineural hearing loss (SNHL).Methods: This was a retrospective cohort study that assessed two groups of infants born between 2014 and 2017. The first group consisted of infants born between 33 and 42 weeks gestation and the second group, of infants born before 33 weeks gestation. Targeted CMV screening was performed in the first group who either failed neonatal hearing screen or were growth retarded. Universal screen was performed in the second group of infants. CMV DNA was tested in urine samples using real time PCR soon after birth.Results: In the first group, 2078 infants were assessed, 19 (0.9%) were found to be CMV positive and in 9 (42%) valganciclovir treatment was initiated. In the second group, out of 549 urine samples/infants, none was positive for CMV DNA soon after birth.Conclusions: A joint strategy of targeted CMV screening in infants who fail hearing screen test with universal screen of premature infants can select infants at risk of hearing impairment due to congenital CMV soon after birth, allows for timely initiation of treatment and prevents dilemmas regarding congenital CMV diagnosis in infants who fail hearing screen in a later age until universal screen will be widely adopted.

Maternal Chronic Hypertension Elevates the Risk for Long-Term Selected Endocrine and Metabolic Morbidity in the Offspring, Particularly Childhood Obesity.

Background: Maternal hypertensive disorders during pregnancy are known to be associated with high rates of perinatal complications for both mother and child. We aimed at determining whether maternal chronic hypertension impacts long-term pediatric endocrine and metabolic morbidity. Methods: A population-based, retrospective cohort study was performed. Exposure was defined as the presence of maternal chronic hypertension. Hospitalizations of the offspring up to the age of 18 years involving endocrine and metabolic morbidity were evaluated. A Kaplan-Meier survival curve was employed to compare the cumulative morbidity incidence between both groups (exposed and unexposed offspring). Cox proportional hazards models were used to control for confounders. Results: During the study period, 232,841 singleton deliveries met the inclusion criteria. Of them, 1.1% (n = 2655) were exposed to maternal chronic hypertension during pregnancy. Total hospitalization rate involving endocrine-metabolic morbidities was doubled in the hypertensive group (1% vs. 0.5% in the normotensive group, p < 0.001). Specifically, childhood obesity was significantly more common in offspring of mothers with chronic hypertension (0.7% vs. 0.2%, respectively, p < 0.001). The survival curve demonstrated significantly higher cumulative incidence of total endocrine and metabolic morbidity in the exposed group (log rank p = 0.002). In a Cox regression model, maternal chronic hypertension exhibited an independent association with long-term childhood endocrine or metabolic morbidity (adjusted hazard ratio = 1.5, 95% confidence interval 1.01-2.2, p = 0.045). Conclusions: Maternal chronic hypertension appears to be an independent and a significant risk factor for long-term pediatric endocrine and metabolic morbidity, and specifically for childhood obesity, in the offspring.

Maternal history of recurrent pregnancy loss increases the risk for long-term pediatric respiratory morbidity of the offspring.

BACKGROUND: While the etiology in many cases of recurrent pregnancy loss (RPL) is unclear, recent evidence suggests possible immunological dysfunction, which is also implicated in the pathophysiology of many pediatric respiratory diseases. OBJECTIVE: We sought to investigate whether maternal history of RPL is associated with long-term respiratory morbidity of the offspring. STUDY DESIGN: A population based cohort analysis was performed comparing the risk of long-term respiratory morbidity (up to the age of 18 years) of children born to mothers with and without a history of RPL (defined as two or more losses). Respiratory morbidity included hospitalizations involving a predefined set of ICD-9 codes, as recorded in the hospital medical records. Deliveries occurred between the years 1991 and 2014 in a tertiary medical center. A Kaplan-Meier survival curve was constructed to compare cumulative respiratory morbidity, and a Cox proportional hazards model was used to control for confounders. RESULTS: During the study period, 242 187 newborns met the inclusion criteria; 5% (n = 12 182) of which were offspring to mothers with a history of RPL. Respiratory morbidity was significantly more common in the exposed group (6.0% vs 4.8%, P < .001). Specifically, offspring to mothers with a history of RPL had higher rates of obstructive sleep apnea and asthma (P < .05). The Kaplan-Meier survival curve exhibited a higher cumulative incidence of total respiratory morbidity in offspring of mothers with a history of RPL (Log rank P < .001). In the Cox regression, maternal history of RPL was independently associated with increased pediatric respiratory morbidity of the offspring with an adjusted hazard ratio of 1.24 (95 % confidence interval [95%CI], 1.15-1.34, P < .001). CONCLUSION: Maternal history of RPL is associated with a higher risk of future pediatric respiratory morbidity of the offspring; possibly explained by a common immunological etiology.

A History of Large for Gestational Age at Birth and Future Risk for Pediatric Neoplasms: A Population-Based Cohort Study.

OBJECTIVE: The aim of this study was to evaluate the association between large for gestational age (LGA) at birth and future risk of childhood neoplasm. STUDY DESIGN: a population-based cohort to compare the long-term risk (up to the age of 18 years) of childhood neoplasms (benign and malignant) in children that were born LGA vs. those that were appropriate for gestational age (AGA), between the years 1991-2014. Childhood neoplasms diagnosis were defined according to international classification of disease 9 (ICD-9) codes recorded medical files. Kaplan-Meier survival curves were used in order to compare cumulative incidence of oncological morbidity over the study period. The Cox proportional hazards model was used to control for confounders. RESULTS: 231,344 infants met the inclusion criteria; out of those 10,369 were diagnosed LGA at birth. Children that were LGA at birth had a higher incidence of leukemia (OR 2.25, 95%CI 1.08-4.65, p = 0.025) as well as kidney tumors (OR = 4.7, 95%CI = 1.02-21.9, p = 0.028). In addition, cumulative incidence over time of childhood malignancies, leukemia, and kidney tumors were significantly higher in LGA children (Log Rank = 0.010, 0.021, and 0.028, respectively). In a Cox regression model controlling for other perinatal confounders, LGA at birth remained independently associated with an increased risk for childhood malignancy (adjusted HR 1.51, 95%CI 1.02-2.23, p = 0.039). CONCLUSION: LGA at birth is associated with increased long-term risk for childhood malignancy and specifically leukemia and kidney tumors. This possible link may help to improve current knowledge regarding potential exposures that are associated with childhood cancer development.

Low Apgar score in term newborns and long-term infectious morbidity: a population-based cohort study with up to 18 years of follow-up.

Since introduced, the Apgar score has remained the most widespread predictor for neonatal morbidity and mortality. We aimed to investigate the association between low 5-min Apgar score and long-term infectious pediatric morbidity. A population-based cohort analysis was performed comparing total and specific subtypes of infectious morbidity leading to hospitalization among term newborns with normal (≥ 7) and low (< 7) 5-min Apgar scores, born between 1999 and 2014 at a single tertiary regional hospital. Infectious morbidity included hospitalizations involving a pre-defined set of infection-related ICD-9 codes. A Kaplan-Meier survival curve was constructed to compare cumulative infectious morbidity incidence and a Cox proportional hazards model to adjust for confounders. The long-term analysis of 223,335 children (excluding perinatal death cases) yielded 585 (0.3%) infants with low 5-min Apgar scores. The rate of infection-related hospitalizations was 9.8% and 12.4% among newborns with normal and low 5-min Apgar scores, respectively (p = 0.06). Adjusting for maternal age, gestational age, hypertension, diabetes, cesarean delivery, and fertility treatments, the association proved to be statistically significant (adjusted HR = 1.28; 95% CI 1.01-1.61).Conclusion: Term infants with low 5-min Apgar scores may be at an increased risk for long-term pediatric infectious morbidity.What is Known:• Though not meant to be a prognostic tool for long-term morbidity, studies assessing the correlation between low Apgar score and long-term outcomes were and are being performed, reporting significant associations with many outcomes-such as cerebral palsy (CP), ophthalmic disorders, GI disorders, and several types of malignancies.• Yet, an association between low Apgar scores and future health remains a matter of controversy.What is New:• Our work shows that a low 5-min Apgar score is independently associated with long-term pediatric infection-related hospitalizations among term singleton newborns.

Unplanned Out-of-Hospital Birth-Short and Long-Term Consequences for the Offspring.

The unpredictable nature of childbirth infrequently results in unplanned out-of-hospital birth, in a pre-hospital setting. We evaluated the perinatal and long-term outcome of children accidentally born out-of-hospital. This was a population-based analysis of singleton deliveries occurring at a single tertiary hospital. The maternal characteristics and pregnancy outcome of unplanned out-of-hospital births were compared with in-hospital attended deliveries. Long-term cumulative incidence of hospitalizations (up to 18 years) involving respiratory, neurological, endocrine or infectious morbidity were evaluated using Kaplan-Meier survival curves and Cox regression models were used to control for confounders. In total, 243,682 deliveries were included, and 1.5% (n = 3580) were unplanned out-of-hospital births. Most occurred in multiparous women, and about a quarter of these women had inadequate prenatal care. Perinatal mortality rate was significantly higher for out-of-hospital births as compared with in-hospital births (OR = 2.9; 95% CI 2.2-3.8, p < 0.001). Kaplan-Meier survival curves demonstrated a significantly lower cumulative incidence of hospitalizations of children born out-of-hospital and the Cox models showed that hospitalization rates involving any of the above morbidities were significantly lower in children born out-of-hospital. While perinatal mortality was higher in unplanned out-of-hospital births, offspring born out-of-hospital showed a lower incidence of hospitalizations involving a variety of morbidities, possibly owing to under-utilization of healthcare services in this population.

Maternal obesity and long-term neuropsychiatric morbidity of the offspring.

OBJECTIVE: To evaluate the long-term pediatric neuropsychiatric morbidity of children born to obese patients. STUDY DESIGN: A population-based cohort analysis was performed comparing all deliveries of obese (maternal pre-pregnancy body mass index of 30 kg/m2 or more) and non-obese patients between 1991 and 2014 at a single tertiary medical center. Hospitalizations of the offspring up to the age of 18 years involving neuropsychiatric morbidities were evaluated according to a pre-defined set of ICD-9 codes, including autistic, eating, sleeping and movement disorders, cerebral palsy, developmental disorders, and more. A Kaplan-Meier survival curve was used to compare cumulative hospitalization rate in exposed and unexposed offspring. A Cox regression model was used to control for confounders. RESULTS: During the study period, 242,342 deliveries met the inclusion criteria. Of them, 3290 were children of obese mothers. Hospitalizations involving neuropsychiatric morbidities were higher in children born to obese mothers compared with those born to non-obese mothers (3.95% vs. 3.10%, p < 0.01). Specifically, offspring of obese mothers had higher rates of autism spectrum disorders and psychiatric disorders. The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of neuropsychiatric-related hospitalizations in the obese group (Fig. 1, log rank p < 0.05). Using a cox proportional hazard model, controlling for maternal age, preterm labor, maternal diabetes, hypertensive disorders of pregnancy, and birthweight, maternal obesity was found to be independently associated with long-term neuropsychiatric morbidity of the offspring (adjusted HR 1.24, 95% CI 1.04-1.47, p < 0.05). CONCLUSION: Maternal obesity is an independent risk factor for long-term neuropsychiatric morbidity of the offspring.

Preterm prelabor rupture of membranes prior to early preterm delivery elevates the risk of later respiratory-related hospitalizations in the offspring.

OBJECTIVE: Preterm prelabor rupture of membranes (PPROM) precedes 30%-40% of all preterm births. Early preterm delivery (<34 gestation weeks) is a well-established risk factor for short- and long-term respiratory morbidity in the offspring. We aimed to ascertain whether the presence of PPROM, before early preterm delivery, independently impacts long-term respiratory hospitalizations in the offspring. STUDY DESIGN: A population-based retrospective cohort analysis was performed including all singleton early preterm deliveries. Exposure was defined as the presence of PPROM. Hospitalizations of the offspring up to the age of 18 years involving respiratory-related morbidity were evaluated. A Kaplan-Meier survival curve and multivariable Cox regression model were used to assess the association. RESULTS: During the study period, 3309 early preterm deliveries met the inclusion criteria. In 22.4% of cases (n = 742), PPROM was documented. Rates of respiratory-related hospitalizations of the offspring up to the age of 18 years were significantly higher in the exposed group (12.5% vs 9.4% in the unexposed group, P = .023). The survival curve demonstrated significantly higher cumulative incidence of respiratory hospitalizations in the exposed group (logrank P = .018). In the Cox regression model controlled for gestational age, and other clinically relevant confounders - PPROM before early preterm deliveries was independently associated with an increased risk for long-term childhood respiratory-related hospitalizations in the offspring (adjusted hazard ratio 1.40, 95% confidence interval, 1.05-1.87, P = .021). CONCLUSION: Fetal exposure to PPROM before early preterm delivery was associated with an increased risk for long-term respiratory hospitalizations in the offspring.

In utero exposure to pre-eclampsia as an independent risk factor for long-term respiratory disease.

INTRODUCTION: Pre-eclampsia has a considerable effect on the intrauterine environment, yet not much is understood about how this impacts the respiratory health of the offspring. The aim of the present study is to determine if pre-eclampsia correlates with a higher incidence of respiratory disease in the offspring. METHODS: This cohort study assessed the differences in respiratory disease patterns between singletons born to mothers with and without pre-eclampsia. The study was conducted between 1991 and 2014 in a regional tertiary medical center. A generalized estimating equation (GEE) model was used to control for confounders and maternal clusters. RESULTS: 253 808 deliveries were included in the study. Of these, 3.0% were to mothers diagnosed with pre-eclampsia (n = 7660), 0.9% with severe pre-eclampsia (n = 2366), and 0.03% with eclampsia (n = 81). A significant linear association was noted between the severity of the pre-eclampsia (no pre-eclampsia, mild, severe pre-eclampsia, and eclampsia) and respiratory disease of the offspring (5.7%, vs 6.0% vs 7.3% vs 9.9%, respectively; P = .003). The offspring of mothers who developed pre-eclampsia had significantly higher rates of asthma (1.1%, vs 1.3% vs 1.4% vs 1.2% correspondingly; P = .018). In the GEE model, controlling for gestational diabetes, maternal age, gestational age, and length of follow up, pre-eclampsia was found to be an independent risk factor for respiratory morbidity in the offspring (adjusted odds ratio = 1.32; 95% confidence interval, 1.21-1.45). CONCLUSION: Exposure to maternal pre-eclampsia is an independent risk factor for long-term respiratory morbidity in the offspring. Specifically, the prenatal exposure to pre-eclampsia was significantly associated with asthma of the offspring.

Isolated oligohydramnios and long-term neurological morbidity of the offspring.

This study aimed to assess the association between maternal-isolated oligohydramnios (IO) and offspring long-term neurological complications. A population-based retrospective cohort study was conducted, including all births at a single tertiary medical center in Israel between the years 1991 and 2014. Multiple pregnancies and potential pregnancy complications associated with oligohydramnios were excluded. The computerized obstetrical database was linked with the computerized dataset of all pediatric hospitalizations of the same medical center. Evaluation of cumulative neurological-associated hospitalizations rate over time was compared using a Kaplan-Meier survival curve. The Weibull survival parametric model was conducted to assess the neurological-associated hospitalization risk in the presence of IO, while accounting for potential confounders. A total of 190,259 pregnancies were included in the study, of which 4063 (2.13%) pregnancies were complicated with IO. Total neurological-related hospitalizations were significantly more common in the IO group (3.7% in the IO group and 3.0% in the comparison group, p = 0.005). Pervasive developmental disorder, movement disorders, developmental disorders, and degenerative and demyelization disorders were all specific neurological diagnoses significantly more common in the exposed group. The survival curve demonstrated a significantly higher cumulative hospitalization rate in the exposed group (log-rank p = 0.001). Using a multivariate model adjusting for gestational age, maternal age, and labor induction, an independent association between IO and long-term neurological morbidity of the offspring was observed (adjusted hazard ratio 1.203; 95% CI 1.02-1.42). In summary, a significant association was found between pregnancies complicated by IO and long-term neurological morbidity of the offspring.