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..

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.

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.

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.

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.

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.

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.

Long-Term Cardiovascular Morbidity in Children Born Following Fertility Treatment.

OBJECTIVE: To determine the risk of long-term cardiovascular disease (CVD) among children born following in vitro fertilization (IVF) and compared with spontaneous pregnancies. STUDY DESIGN: A population-based cohort study including all singleton deliveries occurring between 1991and 2014 at a tertiary medical center was performed. Hospitalizations up to the age of 18 years involving CVD were evaluated in children delivered following IVF, ovulation induction, and spontaneous pregnancies. CVD included valvular disorders, hypertension, arrhythmias, rheumatic disease, cardiomyopathy, ischemic heart disease, and heart failure. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence, and a Cox regression model controlled for confounders. RESULTS: During the study period, 242 187 singleton deliveries met the inclusion criteria; 1.1% following IVF (n = 2603), and 0.7% following ovulation induction (n = 1721). Hospitalizations up to the age of 18 years involving CVD (n = 1503) were comparable in children delivered following IVF (0.6%), ovulation induction (0.7%), and spontaneous pregnancies (0.6%; P = .884). No significant difference in the cumulative incidence of CVD was noted between the groups (log rank P = .781). Controlling for maternal age, gestational age, birthweight, maternal diabetes, and hypertensive disorders in pregnancy, fertility treatment was not noted as a risk factor for long-term pediatric CVD (IVF adjusted hazard ratio 1.05, 95% CI 0.63-1.74, P = .86; ovulation induction adjusted hazard ratio 0.97, CI 95% 0.55-1.71, P = .92). CONCLUSIONS: Singletons conceived via fertility treatments do not appear to be at an increased risk of long-term pediatric CVD.

Placental abruption and long-term neurological hospitalisations in the offspring.

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.

Analysis of Mortality among Neonates and Children with Spina Bifida: An International Registry-Based Study, 2001-2012.

BACKGROUND: Medical advancements have resulted in better survival and life expectancy among those with spina bifida, but a significantly increased risk of perinatal and postnatal mortality for individuals with spina bifida remains. OBJECTIVES: To examine stillbirth and infant and child mortality among those affected by spina bifida using data from multiple countries. METHODS: We conducted an observational study, using data from 24 population- and hospital-based surveillance registries in 18 countries contributing as members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Cases of spina bifida that resulted in livebirths or stillbirths from 20 weeks' gestation or elective termination of pregnancy for fetal anomaly (ETOPFA) were included. Among liveborn spina bifida cases, we calculated mortality at different ages as number of deaths among liveborn cases divided by total number of liveborn cases with spina bifida. As a secondary outcome measure, we estimated the prevalence of spina bifida per 10 000 total births. The 95% confidence interval for the prevalence estimate was estimated using the Poisson approximation of binomial distribution. RESULTS: Between years 2001 and 2012, the overall first-week mortality proportion was 6.9% (95% CI 6.3, 7.7) and was lower in programmes operating in countries with policies that allowed ETOPFA compared with their counterparts (5.9% vs. 8.4%). The majority of first-week mortality occurred on the first day of life. In programmes where information on long-term mortality was available through linkage to administrative databases, survival at 5 years of age was 90%-96% in Europe, and 86%-96% in North America. CONCLUSIONS: Our multi-country study showed a high proportion of stillbirth and infant and child deaths among those with spina bifida. Effective folic acid interventions could prevent many cases of spina bifida, thereby preventing associated childhood morbidity and mortality.

Maternal recurrent pregnancy loss is associated with an increased risk for long-term neurological morbidity in offspring.

AIM: To determine whether maternal history of recurrent pregnancy loss (RPL) impacts on the long-term neurological health of the offspring. METHOD: A population-based cohort analysis was performed, including all singletons born between 1991 and 2014 at a single regional tertiary centre. Neurological morbidity up to age 18 years (including cognitive, motor, and psychiatric disorders) in children born to mothers with and without a history of RPL was compared. Cumulative neurological morbidity incidence was compared with survival curves and a Weibull multivariable survival model to control for follow-up time and relevant confounders. RESULTS: A total of 242 187 deliveries met the inclusion criteria during the study period, 5% (n=12 182) of which were in mothers with RPL. Epilepsy and developmental disorders were significantly more common in the group with RPL (0.95 vs 0.74/1000 person-years [p=0.009] and 0.22 vs 0.09/1000 person-years [p<0.001]). The survival curves demonstrated significantly higher cumulative incidences of epilepsy and developmental disorders in the group with RPL. The multivariable model exhibited an independent association between maternal RPL and childhood epilepsy (adjusted hazard ratio 1.23; 95% confidence interval 1.01-1.50) and developmental disorders in the offspring (adjusted hazard ratio 2.41; 95% confidence interval 1.60-3.64). INTERPRETATION: A history of maternal RPL appears to be independently associated with long-term neurological morbidity of the offspring. WHAT THIS PAPER ADDS: Hospitalizations for epilepsy and developmental disorders are significantly more common among children of mothers with a history of recurrent pregnancy loss.

Apgar score and long-term respiratory morbidity of the offspring: a population-based cohort study with up to 18 years of follow-up.

The objective of this study is to investigate whether a significant association exists between low 5-min Apgar scores (< 7) and respiratory morbidity of the offspring. A population-based cohort analysis was performed comparing subtypes of respiratory morbidity leading to hospitalizations among children (up to age 18 years) stratified by their 5 min Apgar scores. Data were collected from two databases of a regional tertiary center. All singleton deliveries occurring between 1991 and 2014 were included in the analysis. A Kaplan-Meier survival curve was constructed to compare cumulative respiratory-related hospitalization incidence and a Cox proportional hazards model to control for confounders. Deliveries (238,622) met the inclusion criteria. Low 5-min Apgar scores were recorded in 742 (0.3%) newborns. Incidence of respiratory hospitalizations was higher among the low 5 min Apgar score group (7.3 vs. 4.8% in the normal [≥ 7] 5 min Apgar score group; OR = 1.5, 95%CI 1.2-2.0, p = 0.003). Association remained significant in the Cox model (aHR = 1.4, 95%CI 1.1-1.9, p = 0.01). Incidence of respiratory-related hospitalizations in preterm born offspring was higher among the low vs. the normal 5 min Apgar score groups (13.4 vs. 7.2%, OR = 2.0, 95%CI 1.2-3.1 , p = 0.008). Association remained significant in the multivariable analysis (aHR = 1.6, 95%CI 1.1-2.5, p = 0.03). The survival curves demonstrated significantly higher cumulative respiratory morbidity in the low Agar score group for the entire cohort and for the preterm born subgroup.Conclusion: Newborns, of any gestational age, with low 5 min Apgar scores appear to be at an increased risk for pediatric respiratory morbidity. What is Known: • Apgar score is a method for assessment of the medical condition of a newborn, and of the need for medical intervention and/or resuscitation. Studies assesing the correlation between low Apgar score and short or long term outcomes report a sgnificant correlation with different outcomes including neurological development and more. As two of its five components (color and respiratory effort) are utilizing the respiratory status, low Apgar scoreis associated with a higher risk for immedisate respiratory morbidity. What is New: • Low Apgar score increases the chances for several long-term respiratory-related morbidities, independent of gestational age and other obstetrical circumstances.

Long-term endocrine outcome of small for gestational age infants born to mothers with and without gestational diabetes mellitus.

Small for gestational age (SGA) infants and infants born to mothers with gestational diabetes mellitus (GDM) are at an increased risk for significant morbidity and mortality, mainly metabolic disorders. We aimed to question the long-term endocrine morbidity of SGA infants born to mothers with GDM compared to SGA infants born to non- diabetic mothers. A population-based cohort study was performed to assess the risk for endocrine morbidity among children born SGA to mothers with and without GDM. The main outcome evaluated was endocrine morbidity of the offspring up to the age of 18 years, predefined in a set of ICD-9 codes. Endocrine morbidity included thyroid disease, insulin and non-insulin dependent diabetes mellitus, hypoglycemia, childhood obesity, parathyroid hormone disease, adrenal disease, and sex hormone disease. All SGA infants born between the years 1991 and 2014 and discharged alive from the hospital were included in the study. Multiple pregnancies, infants with congenital malformations or chromosomal abnormalities and mothers lacking prenatal care were excluded from the analysis. Kaplan-Meier survival curve was constructed to compare cumulative endocrine morbidity. A Cox proportional hazards model was conducted to control for confounders. During the study period, 9312 newborn infants met the inclusion criteria, of them 259 SGA infants were born to mothers with GDM and 9053 SGA infants were born to mother without GDM. No significant differences in long-term endocrine morbidity were noted between the groups (0.8% in children born to mothers with GDM vs. 0.5% in children born to non-diabetic mothers, p = .62). Likewise, the Kaplan-Meier survival curve did not demonstrate a significantly higher cumulative incidence of endocrine morbidity in offspring of women with GDM (log rank test p=.67). In a Cox regression model, while controlling for ethnicity, hypertensive disorders, preterm birth, and maternal age, delivery of an SGA neonate to mother with GDM was not associated with long-term endocrine morbidity of the offspring (adjusted HR 1.2, 95% confidence interval 0.27-5.00, p=.82). SGA infants born to mothers with GDM are not at an increased risk for long-term endocrine morbidity as compared with SGA infants born to non-diabetic mothers.

Infertility Treatments and Long-Term Neurologic Morbidity of the Offspring.

OBJECTIVE: To determine the risk of long-term neurologic morbidity among children (up to 18 years) born following in vitro fertilization (IVF) or ovulation induction (OI) treatments as compared with spontaneously conceived. STUDY DESIGN: A population-based cohort analysis was performed, including data from the perinatal computerized database on all singleton infants born at the Soroka University Medical Center (SUMC) between the years 1991 and 2014. This perinatal database was linked and cross-matched with the SUMC computerized dataset of all pediatric hospitalizations. RESULTS: Neurologic morbidity was significantly more common in IVF (3.7%) and OI (4.1%) offspring as compared with those following spontaneous pregnancies (3.1%; p = 0.017). In particular, attention deficit/hyperactivity disorders and headaches were more common in the OI group and sleep disorders in the IVF group, whereas autism and cerebral palsy were comparable between the groups. In the Weibull multivariable analysis, while controlling for maternal age, preterm delivery, birthweight centile, maternal diabetes, and hypertensive disorders, IVF (adjusted hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.14-1.71; p = 0.001), but not OI (adjusted HR: 1.17' 95% CI: 0.92-1.48; p = 0.196), was noted as an independent risk factor for long-term pediatric neurologic morbidity. CONCLUSION: IVF offspring appear to be at an increased risk of long-term neurologic morbidity up to 18 years of age.

Offspring of women following bariatric surgery and those of patients with obesity are at an increased risk for long-term pediatric endocrine morbidity.

OBJECTIVE: To assess whether offspring of women following bariatric surgery as well as offspring of obese women are at an increased risk for long-term pediatric endocrine morbidity. SETTING: This study was conducted at the university hospital. METHODS: A population-based cohort study compared the incidence of long-term (up to the age of 18 years) occurrence of endocrine morbidity between offspring of mothers following bariatric surgery and obese mothers, as compared with parturients without obesity and without prior bariatric surgery. RESULTS: During the study period 220,563 newborns met the inclusion criteria; 1001 were delivered by patients following bariatric surgery, 2275 were delivered by obese women and 217,287 were delivered by normal weight women without prior bariatric surgery. Long-term endocrine morbidity was more common in the bariatric group (2.3%) and the obesity group (1.5%) as compared with the comparison group (0.5%; P < 0.001). Specifically, pediatric obesity was significantly more common in children of mothers following bariatric surgery (1.8%) and of mothers with obesity (1.2%) as compared with the comparison group (0.2%; P < 0.001). Children born to women following bariatric surgery as well as obese women had higher cumulative incidence of pediatric endocrine morbidity (Log rank, P < 0.001). The results remained significant when controlling for maternal factors, adjusted HR 6.25, 95% CI 4.10-9.50; P < 0.001 for women following bariatric surgery and aHR 2.40 95% CI 1.69-3.40; P < 0.001 for obese women. CONCLUSION: Offspring of women following bariatric surgery as well as those of obese women are at an increased risk for long-term pediatric endocrine morbidity.

Placental abruption and long-term cardiovascular morbidity of the offspring.

OBJECTIVE: While placental abruption is often associated with short-term adverse pregnancy outcomes, we sought to assess whether placental abruption increases the risk for long-term cardiovascular morbidity of the offspring. METHODS: To study the long-term cardiovascular hospitalizations of offspring of patients with and without placental abruption, cardiovascular morbidity was assessed up to the age of 18 years according to a predefined set of ICD-9 codes associated with hospitalization of the offspring. Our data consist of deliveries which occurred between the years 1991 and 2014 in a tertiary medical center. Pregnancies following fertility treatments, multifetal pregnancies, and pregnancies with offspring with congenital anomalies, lack of prenatal care, and perinatal mortality were excluded from the study. We used Kaplan-Meier curve to compare cumulative morbidity incidence and Cox proportional hazards model to control for confounder. RESULTS: During the study period, we examined 217,910 deliveries, out of which 0.46% (n = 1003) were effected by placental abruption. Compared to normal birth children, children born to mothers with placental abruption did not show a significantly higher cumulative incidence of long-term cardiovascular morbidity (1.0% vs. 0.6%; p = 0.127). Placental abruption was not noted as an independent risk factor for long-term cardiovascular morbidity of offspring in the Cox regression analysis, which adjusted for confounders. CONCLUSION: Our study does not support the association between placental abruption and risk for long-term cardiovascular morbidity of the offspring.

Maternal hypothyroidism and future pediatric neurological morbidity of the offspring.

BACKGROUND: Maternal hypothyroidism in pregnancy has been associated with neurocognitive impairment in exposed children, ranging from psychomotor-developmental delay to lower IQ scores. OBJECTIVE: To investigate the long-term neurological morbidity of children to hypothyroid mothers during pregnancy. STUDY DESIGN: A population-based cohort study was performed including all deliveries occurring in a period of 20 years at a tertiary medical center. We excluded multiple pregnancies, fetuses with congenital malformations, perinatal mortality cases and women lacking prenatal care from the study. Neurological-related hospitalizations of children (up to 18 years) were evaluated using neurological morbidities that were predefined by ICD-9 codes. Kaplan-Meier survival curve was used to compare cumulative hospitalization rate in exposed and unexposed children. A Cox regression model was used to control for confounders. RESULTS: During the study period, 217,910 deliveries met the inclusion criteria. Of them, 1.1% (n = 2403) were in mothers with known hypothyroidism during pregnancy. The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of neurological-related hospitalizations in the hypothyroidism group (log rank p = 0.007). Total hospitalization rate per person years was significantly higher in the maternal hypothyroidism group (5.5 vs. 3.1, HR =1.37, 95% CI 1.10-1.73, p = 0.007). The Cox regression model controlled for various possible confounders including maternal age, maternal obesity, birth weight, preterm birth, maternal diabetes, hypertensive disorders, induction of labor and mode of delivery, found maternal hypothyroidism to be independently associated with pediatric neurological morbidity in these children (adjusted HR =1.33, 95% CI 1.05-1.68, p = 0.01). CONCLUSION: Maternal hypothyroidism in pregnancy is independently associated with long-term pediatric neurological morbidity of the offspring.

Gestational age and the long-term impact on children's infectious urinary morbidity.

PURPOSE: Given the negative impact of prematurity on offspring's health, we sought to determine whether different gestational ages at birth impact differently on the prevalence of childhood infectious urinary morbidity in the offspring. METHODS: In this population-based cohort analysis, all singleton deliveries occurring between 1991 and 2014 at a single regional tertiary medical center were included. Gestational age upon delivery was sub-divided into early preterm (< 34 weeks), late preterm (34-36 6/7 weeks), early term (37-38 6/7 weeks), full term (39-40 6/7 weeks), late term (41-41 6/7 weeks) and post-term (> 42 weeks). Congenital malformations were excluded. Rates of infectious urinary morbidity-related hospitalizations of offspring up to age 18 years were assessed using a survival curve and a Cox multivariable model. RESULTS: During the study period, 238,620 deliveries met the inclusion criteria. Urinary-related hospitalization (n = 1395) rates decreased as gestational age increased, from 1.7% in the early preterm group, 0.9% in the late preterm group, 0.6% in the early-term group and only 0.5% in the full, late and post-term groups (p > 0.001; chi-square test for trends). In the Cox model, controlled for maternal age, preterm as well as early-term deliveries exhibited an independent association with pediatric urinary morbidity as compared with full term (early preterm: aHR-3.305, 95% CI 2.4-4.54; late preterm: aHR-1.63, 95% CI 1.33-1.99; early term: aHR-1.26, 95% CI 1.1-1.43, p = 0.01). CONCLUSIONS: Deliveries occurring at preterm and at early term are independently associated with pediatric urinary morbidity in the offspring. This risk decreases as gestational age advances.

The association between pregnancies complicated with isolated polyhydramnios or oligohydramnios and offspring long-term gastrointestinal morbidity.

OBJECTIVE: Infants born to mothers with pregnancies complicated by polyhydramnios or oligohydramnios are at an increased risk for significant adverse perinatal outcome. We sought to assess whether in utero exposure to amniotic fluid abnormalities increases the risk of long-term gastrointestinal (GI) morbidity in the offspring. METHODS: In a population-based cohort study, the incidence of GI-related hospitalizations was compared between singletons exposed and unexposed to oligohydramnios or polyhydramnios. Deliveries occurred between the years 1991-2014 in a regional tertiary medical center. Offspring GI morbidity was assessed up to the age of 18 years according to a pre-defined set of International Classification of Diseases, ninth revision (ICD-9) codes associated with hospitalization. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence. A Cox proportional hazard model was performed to control for confounders. RESULTS: During the study period, 186,196 newborns met the inclusion criteria, of which 2.1% (n = 4063) and 3.0% (n = 5684) were born following pregnancies with oligohydramnios and polyhydramnios, respectively. The Kaplan-Meier curve demonstrated that children exposed to isolated oligohydramnios (but not to polyhydramnios) had higher cumulative incidence of GI morbidity (log-rank test, p = 0.001). In the Cox regression model, controlled for maternal age, gestational age, birth weight, and mode of delivery, isolated oligohydramnios (adjusted HR 1.2, 95% CI 1.04-1.34, p = 0.007), but not polyhydramnios (adjusted HR 1.1, 95% CI 0.91-1.13, p = 0.766), was found to be independently associated with long-term GI morbidity of the offspring. CONCLUSION: In utero exposure to isolated oligohydramnios is an independent risk factor for long-term GI morbidity in the offspring.

Pediatric Cardiovascular Morbidity of the Early Term Newborn.

OBJECTIVE: To determine whether early term delivery (at 370/7-386/7 weeks of gestation) is associated with long-term pediatric cardiovascular morbidity of the offspring. STUDY DESIGN: A population-based cohort analysis was performed including all term deliveries occurring between 1991 and 2014 at a single tertiary medical center. Gestational age at delivery was subdivided into early term (370/7-386/7), full term (390/7-406/7), late term (410/7-416/7) and post term (≥420/7) delivery. Hospitalizations of children up to the age of 18 years involving cardiovascular morbidity were evaluated, including structural valvular disease, hypertension, arrhythmias, rheumatic fever, ischemic heart disease, pulmonary heart disease, perimyoendocarditis, congestive heart failure, and others. Kaplan-Meier survival curves were used to compare cumulative hospitalization incidence between groups. A multivariable Weibull parametric model was used to control for confounders. RESULTS: During the study period, 223 242 term singleton deliveries met the inclusion criteria. Of them, 24% (n = 53 501) occurred at early term. Hospitalizations involving cardiovascular morbidity were significantly more common in children delivered at early term (0.7%) as compared with those born at full (0.6%), late (0.6%), or post term (0.5%; P = .01). The survival curve demonstrated a significantly higher cumulative incidence of cardiovascular-related hospitalizations in the early term group (log-rank P <.001). In the Weibull model, early term delivery was found to be an independent risk factor for cardiovascular-related hospitalization as compared with full term delivery (adjusted HR, 1.16; 95% CI, 1.01-1.32; P = .02). CONCLUSION: Early term delivery is independently associated with pediatric cardiovascular morbidity of the offspring as compared with offspring born at full term.