P < .001) and in the right index , the DTI-ALPS in ASD patients was significantly lower than that in healthy controls. Furthermore, the DTI-ALPS index was strongly and positively associated with age. In patients with ASD, there is a glymphatic system dysfunction. This is intimately correlated to age. Our findings suggest the importance of the DTI-ALPS approach in assessing the function of the glymphatic system in ASD.This study used diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) to assess glymphatic system function in autism spectrum disorder (ASD) compared to healthy controls. Patients with ASD may have glymphatic system dysfunction, which is related to age. We retrospectively included 30 children with ASD and 25 healthy controls in this study. 3T magnetic resonance imaging scanner was used to perform DTI magnetic resonance imaging on all participants, and the DTI-ALPS index was calculated from the DTI data. Additionally, we evaluated how the DTI-ALPS index differed between the 2 groups. Moreover, we examined the relationships between the bilateral DTI-ALPS index and the age of the participants. The DTI-ALPS index considerably differed between groups. In the left index (1.02 ± 0.12 vs. 1.27 ± 0.25,  The aquaporin-4 water channels allow the flow of cerebrospinal fluid (CSF) into the brain through the perivascular spaces of the leptomeningeal and penetrating arteries and then into the brain interstitial fluid (ISF). The channel then guides flow to the venous perivascular and perineuronal regions, where it eventually reaches the lymphatic drainage arteries of the meninges and cervical spine. The glymphatic system is a vital system for removing protein waste products from the brain. CSF removes waste proteins from the tissue as it reaches the interstitial space.,4 The CSF-ISF fluid, mixed with interstitial waste solutes, is then carried to the large central veins’ perivenous compartment, where it exits into lymphatic vessels and the systemic circulatory system.,5,6 The glymphatic system is more activated during slow-wave sleep than during awake.,7The glymphatic system is a well-organized system for transporting fluids.–11 Clinical imaging of the glymphatic system in humans is a new field among these imaging techniques. Recently, several novel approaches for evaluating the glymphatic system in humans have been developed. Brain MRI is an excellent technique for whole-brain research since it can reveal deep brain regions.Brain section microscopy, 2-photon microscopy, transcranial mesoscopic imaging, and proton emission tomography-magnetic resonance imaging (MRI) have all been used to visualize the glymphatic system. It measures the diffusivity using the diffusion tensor method to determine the mobility of water molecules in the direction of the perivascular space. It is based on the fact that the perivascular space, as well as the medullary veins, are orthogonal to the projection and association fibers at the level of the lateral ventricle body. The projection and association fibers will be affected by glymphatic system malfunction with histological alterations.,12 Because the DTI-ALPS approach is noninvasive and does not require gadolinium-based contrast delivery, it can be used in routine clinical settings.,13Diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) has been proposed as a glymphatic means product.,14–19 Furthermore, the DTI-ALPS approach has never been used to investigate the function of the glymphatic system in individuals with autism spectrum disorder (ASD).Given the novelty of the glymphatic system concept, a growing number of studies have been published to better understand the role of the glymphatic system in neurological disorders such as sleep behavior disorder, diabetes, temporal lobe epilepsy, Alzheimer’s disease, Parkinson’s disease, normal pressure hydrocephalus, and other neurological illnesses. In early childhood, when the symptoms first appear, the illness is typically assumed to last a lifetime. For many years, autism was believed to be a rare condition after it was first identified in 1943 by Leo Kanner. However, during the last few decades, the estimated prevalence has substantially and persistently climbed. This is believed to be the result of several variables, such as the expansion of illness mechanisms, some novel pathophysiological detection, and increasing awareness and knowledge of the disorder. There might also be more factors which are currently unknown and subjected to much conjecture. The Centers for Disease Control and Prevention (CDC) currently estimated that 1 in 68 children are diagnosed with ASD with a male-to-female ratio of 4:1, resulting in numbers of 1 in 42 boys and 1 in 189 girls. Despite significant research, the cause and the precise pathophysiology of this glymphatic system dysfunction remain largely unknown.ASD is a complex, heterogeneous neurodevelopmental disease characterized by repetitive activities, constrained interests, and impairments in social communication and reciprocity. thus it may have clinical significance.,24 Therefore, this study aimed to compare the glymphatic system function in ASD patients to that in healthy controls using the DTI-ALPS method. However, no previous study has investigated the relationship between VRs and ASD in children. Moreover, it is uncertain whether VRs alterations show a correlation with age. To validate changes in glymphatic system function, the correlations of bilateral ALPS index of children with ASD were studied. We hypothesized that ASD has severe glymphatic system malfunction and that the ALPS index is positively related to age. The findings from this study will change the understanding of the mechanism of the disease.Currently, the mechanism underlying ASD remains unclear. However, previous studies have demonstrated that dilation of the Virchow-Robin space (VRs) in the cerebral convexities is increased in the ASD group and associated with developmental delay,The local institutional review board, the Clinical Research Ethics Committee of Yan’an University, Affiliated Hospital (No. YUSMAFEC2017RC-026), examined and approved this retrospective case–control study. The children’s parents were aware of the potential risks of an MRI examination, such as loud noise, as well as the side effects of oral chloral hydrate. The parents had given written informed consent. gestational age of 37 weeks or more; and no history of brain injury, head trauma, or central nervous system infections. The total number of families invited to participate was 84, and they gave informed consent. The following were the criteria for exclusion: incomplete clinical information; intracranial infection; head trauma; diagnosed with other psychological diseases; MRI abnormalities, such as hyperintensity on T2 fluid-attenuated inversion recovery (FLAIR) ; hearing loss; and cerebral palsy. The following criteria were used to enroll children in the control group: children with a gestational age of 37 weeks or more; There is no history of seizures; and there are no MRI abnormalities. Children whose images revealed artifacts were not allowed to participate. Children with neurological problems  and intracranial infection were also excluded from the study, as shown in Fig. Patient participants diagnosed with ASD, who completed MRI examinations as part of the screening for brain disorders, were sampled for the present study. Participants were recruited from a consecutive case series of children (aged 24–72 months) assessed at the Neuropsychiatric Child Unit of the Yan’an University, Affiliated Hospital, over the course of 4 years 2017–2021). Inclusion criteria were: clinical diagnosis of ASD, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria of the American Psychological Association (APA 2000);7–2021. I2; number of b0 = 8; TR/TE = 11,000/69.5 ms; slice thickness = 2.5 mm without spaces; field of vision = 240 mm; and matrix size = 128.At the Yan’an University Affiliated Hospital, all subjects completed MRI examinations using the same 3.0-T scanner  with an 8-channel head coil. All children were adjusted while sleeping to eliminate motion artifacts and facilitate the MRI examination. Hearing protection was provided by micro-earplugs, while head immobilization was provided by molded foam. The 3.0-T scanner was used to perform 3-dimensional rapid spoiled gradient-recalled echo T1-weighted imaging (T1WI), fast spin-echo (FSE) T2-weighted imaging (T2WI), T2 FLAIR, and single-shot echo-planar DTI. The parameters of MRI sequences  were the same for all participants. T2WI was used to assess VRs, and T1WI and T2-FLAIR were utilized to distinguish VRs from other lesions. The following were the parameters of the MRI sequences: (i) T2WI: TR/TE = 4200/120 ms; slice thickness = 4 mm without gap; field of vision = 240 mm; and matrix size = 320 × 320. (ii) DTI: 30 gradient directions; b values = 0 and 600 s/mmhttp://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FDT). Image processing and comparison of ALPS indexes among ASD and control groups were addressed using an optimized protocol as described in previous studies.–29The FMRIB software library was used for processing DTI data. First, an eddy current correction was performed for all the DTI of all subjects. Then, the brain regions were extracted using the FMRIB software library Brain Extraction Tool  was utilized. P < .017 was determined to be statistically significant using the Bonferroni correction, and multiple comparisons were made across the groups.To compare demographic data between ASD and the control group, the Mann–Whitney The hospital-based study eventually enrolled 55 patients based on the inclusion and exclusion criteria: 30 in the ASD group and 25 in the control group. ASD and control groups had no significant differences in age, sex, or gestational age Table .P < .001) index and in the right index . The bilateral index in patients with ASD was significantly lower than in healthy controls.Between patients with ASD and healthy control, there were significant differences in DTI-ALPS index along the z-axis along projection fibers and the y-axis along association fibers Table . The indThe DTI-ALPS index was significantly positively correlated with age in ASD , and in control  as shown in Fig. In this study, we found that patients with ASD had significantly lower ALPS index than healthy controls, suggesting that patients with ASD have glymphatic system dysfunction. In addition, ALPS index was positively correlated with age in patients with ASD, which demonstrates that the glymphatic system function declines in patients with ASD. Our hypothesis was confirmed by these findings. In the ASD brain, poor interstitial solute clearances and aberrant CSF-ISF communication can be seen. As a result of the breakdown of blood–brain barrier (BBB) integrity caused by an ictal event, serum solute shifts locally in the brain parenchyma, and changes in ISF ionic composition cause water retention. Long-term pathological alterations may alter ISF flow, resulting in a slowed clearance system and hazardous chemical buildup in the brain. Phosphorylated tau is dispersed across cortical neurons, perivascular areas around penetrating pial arteries, and meninges in ASD patients, and extracellular phosphorylated tau is also distributed parallel to venules. The distribution of phosphorylated tau in the brain differs from that of extravasation markers such as immunoglobulin G or albumin. Furthermore, perivascular phosphorylated tau does not extend radially from the vessel but rather follows longitudinal para-vascular tracks, implying that high phosphorylated tau is associated with inefficient waste clearance from the brain.Many investigations on neurological illnesses have recently been undertaken as a result of the growing interest in the glymphatic system. Reduced amyloid clearance is linked to the pathogenesis of Alzheimer’s disease, and phosphorylated Tau clearance is linked to chronic traumatic encephalopathy.,37 In this study comparing the DTI-ALPS index between patients with ASD and control, the ASD group had a lower DTI-ALPS index than the control group. A recent study looked at the DTI-ALPS index in epileptic patients and found that individuals with epilepsy who also had moderate cognitive impairment or dementia had a considerably lower DTI-ALPS index than healthy controls. The DTI-ALPS index was considerably lower in patients with temporal lobe epilepsy than in healthy control. As a result, it’s important to consider the possibility of using a novel biomarker to noninvasively evaluate glymphatic function in patients with ASD.In numerous neurodegenerative illnesses, the DTI-ALPS approach was utilized to assess glymphatic system function. A substantial association between the glymphatic and the VRs volume and counts was discovered in a study of patients with epilepsy and simple febrile seizures.,39,40 Previous studies have found broad changes in cortical thickness, subcortical volumes, and cerebral white matter in epileptic patients. Furthermore, the changed patterns varied among epileptic syndromes.–43 An increased number of activated microglia was found in postmortem brain tissue from epileptic individuals, with enhanced fractions of microglia differing depending on cortical thickness. More research is needed to look into the changes in glymphatic system function in ASD. In this study, the DTI-ALPS index showed a significant positive correlation between age in patients with ASD and healthy controls. Glymphatic system impairment in ASD has been linked to loss of perivascular aquaporin-4 polarization and BBB malfunction. The aggregation of misfolded proteins in numerous neurodegenerative illnesses exacerbates the impaired distribution of growth factors, neuromodulators, carrier proteins, and other solutes due to glymphatic system malfunction. The effect of seizure length on the glymphatic system may be connected to changes in BBB distribution and clearance in the brain parenchyma, as previously indicated. Thus, we predicted that the DTI-ALPS index would differ depending on the duration of ASD, among other clinical parameters; instead, the DTI-ALPS index was significantly inversely correlated with age. However, we find significant differences in the DTI-ALPS index between patients with ASD and healthy controls, suggesting that there are changes in glymphatic system function in ASD. This finding was inconsistent with the finding from a previous study showing glymphatic system dysfunction in patients with focal epilepsy. This difference may come from the fact that we only included patients with ASD in the fast-developing brain age range, while previous studies did not include such an age range. We interpret the positive correlation of DTI-ALPS index and age as potential signs of global DTI parameters associated with poor glymphatic system function in our patients. This is the first study to investigate glymphatic system function in children with ASD. However, this work has some limitations, although we were able to demonstrate glymphatic system failure in ASD. For instance, the sample size was tiny, and the study was not multicentric. In the scan protocol, we used a relatively low b value (600 s/mm2), which may have difficulties to differentiate between DTI-ALPS and CSF. Also, we manually drew the ROIs and measured diffusivity along the axis at each of the 3 fibers, which could have resulted in differences across measurements. However, initially, we used a different hue of DTI to identify each fiber. Furthermore, we collected fiber orientation and diffusivity at the voxel level at the region of interest, and then chose one voxel for each fiber with maximum orientation on the same x-axis, potentially improving the accuracy of fiber detection.Using the DTI-ALPS method, previous studies on epilepsy have shown that patients with juvenile myoclonic epilepsy, temporal lobe epilepsy and focal epilepsy have significant glymphatic system dysfunction.We was able to demonstrate glymphatic system dysfunction in patients with ASD. Furthermore, glymphatic system malfunction is intimately correlated to age. Thus, our findings help to understand how DTI-ALPS can be used as a potential biomarker in ASD to increase the probability of diffusion alterations, emphasizing the necessity of their therapy. Our findings suggest that the DTI-ALPS approach may help assess the function of the glymphatic system in ASD.We appreciate the contribution of our patients and their families for participating in this study.Conceptualization: Xin Li.Methodology and writing and original draft: Cailian Ruan.Editing: Abdoulaye Issotina Zibrila.Review: Mazen Musa.Software: Yifan Wu.Validation: Zhang Zhengxiang.Funding acquisition: Heng Liu.Supervision and final validation: Mustafa Salimeen.


Early forecasts give people in a storm’s path time to prepare. Less is known about the cost to society when forecasts are incorrect. In this observational study, we examine over 700,000 births in the path of Hurricane Irene and find exposure was associated with impaired birth outcomes. Additional warning time was associated with decreased preterm birth rates for women who experienced intense storm exposures documenting a benefit of avoiding a type II forecasting error. A larger share of this at-risk population experienced a type I forecasting error where severe physical storm impacts were anticipated but not experienced. Disaster anticipation disrupted healthcare services by delaying and canceling prenatal care, which may contribute to storm-impacted birth outcomes. Recognizing storm damages depend on human responses to predicted storm paths is critical to supporting the next generation’s developmental potential with judicious forecasts that ensure public warning systems mitigate rather than exacerbate climate damages. Early forecasts give people in a storm’s path time to prepare, but less is known about the cost to society when forecasts are incorrect. In this observational study, the authors examine over 700,000 births in the path of Hurricane Irene and find exposure was associated with impaired birth outcomes. Despite the physical damages from these storms totaling over 500 billion dollars since 2004, National Oceanic and Atmospheric Administration (NOAA) National Hurricane Center (NHC) funding allocated to forecasting tropical storm threats continues to diminish4. Media coverage supports advanced warning systems by forecasting potential threats to the masses. The goal of disaster forecasts is to avert damages to infrastructure, human health and well-being while recognizing that the broadcast itself will increase psychological stress in viewing populations5. Yet, no large-scale study exists documenting the relationship between forecast accuracy and human health impacts in hurricane-threatened populations.The best available climate science predicts an increase in high-intensity7. New evidence reveals that forecasted posttraumatic stress symptoms, leading up to a hurricane event, influences the public’s mental health before and after a hurricane event5. Taken together, NHC storm forecasts, such as the “Cone of Uncertainty,” which are often misinterpreted by the public8 but widely disseminated by the media, may cause substantial distress to viewing populations. Such a public health threat is most preventable in communities that expect and prepare for a hurricane exposure that does not end up generating physical impacts, i.e., a type I forecasting error.The release of highly uncertain disaster forecasts may represent a public health threat for several reasons. Disaster-related media coverage has long been shown to contribute to posttraumatic stress disorder symptoms in viewers12 and disrupt access to healthcare services16, which may have long-run implications for the unborn child’s livelihood18. In utero exposure to stress12, environmental toxins20 and disrupted access to health services21 are leading explanations for observed reductions in birth weight and gestation lengths. In the context of tropical storms, in utero exposures have also led to abnormal conditions of the newborn baby 22. Causal linkages between these birth outcomes and later life disease prevalence24, mental health12, aptitude, educational attainment and future wages17 have been established. No study to date has isolated these underlying mechanisms empirically and measured the extent to which institutions influence birth outcomes by disseminating uncertain disaster forecasts to the public.Experiencing a disaster during pregnancy can impair birth outcomesThe purpose of this study is twofold. First, we investigate empirically the impact of in utero exposure to Hurricane Irene on a variety of birth outcomes, including birth weight, gestation length and incidence of low birth weight and preterm birth outcomes. The sample focuses on more than 700,000 births in representative communities across North Carolina  in parentheses. The estimated birth impacts were overlayed with a cumulative distribution of wind speed exposures in order to visually explore the association between estimated birth outcomes and wind intensity Fig. . The avends Fig. .Fig. 1EsGestation lengths were also shortened following in utero exposure by an average of 0.10 weeks (0.07–0.14 weeks), which represented a 0.18–0.36% reduction on the gestation length sample mean  Fig. . The inc15) Fig. . The inc02) Fig. . The inc29) Fig. .30. While these samples were not taken from the same residences of our pregnant women sample, both data sets had statewide and residence-level coverage and used the same selection into treatment window around Hurricane Irene. We found no meaningful relationship between storm exposure intensity and private well water contamination rates at the Environment Protection Agency’s recommended maximum contaminant load level  and the total number of prenatal care visits that occurred throughout the pregnancy . The average in utero exposure to Hurricane Irene was associated with a delayed first prenatal care appointment by 0.24 months (0.18–0.30 months), which represented an approximate 1 week or 6.92–11.54% delay on the sample mean of when prenatal care was initiated  Fig. . The tot21) Fig. . SimilarThe average individual that received heavy rainfall experienced an average of 15.9 6-h periods within Hurricane Irene’s cone of uncertainty (approximately 95 h). For these individuals, the prediction of direct hurricane exposure was ex post correct and additional time spent within the cone of uncertainty served as an accurate risk signal to prepare for imminent exposure. We found that the marginal effect of an additional 6-h window of preparation for these heavily exposed populations had no meaningful impact on birth outcomes, gestation length or the incidence of low birth weight, very low birth weight or extreme preterm birth outcomes . For these individuals, the prediction of direct hurricane exposure was ex post incorrect and additional time spent within the cone of uncertainty served as an inaccurate risk signal that may have disrupted unnecessarily planned healthcare services. We found that the marginal effect of residing within the cone for an additional 6-h window was associated with decreased birth weights by 4.1 g for this lightly exposed population, which represented a 0.13% reduction in birth weight on the lightly exposed sample mean .31 relied on private wells that were federally unregulated and particularly vulnerable to contamination from severe weather and flooding events35. We found no evidence that birth impacts were driven by direct physical impacts of Hurricane Irene  or indirect physical exposures .We might expect that statewide groundwater contamination would explain the observed birth impacts. During Hurricane Irene, over 2 million individuals that represented over 20% of North Carolina’s populationWe further found no evidence that the observed birth impacts were explained by a systematic geographic sorting along socioeconomic lines, which may have occurred during our sample window. In such a case, we would expect prediagnosed medical risk factors to vary systematically between our treatment and control groups. Importantly, we observed evidence that hurricane exposure created prenatal care disruptions that varied little across the intensity of storm exposures. Such a finding suggests that the anticipation of hurricane exposures and associated institutional responses to that anticipation, rather than the physical direct and indirect impacts from the storm itself, may be a key factor.22. Consistent with the broader disasters literature12, we build on22 with clear evidence that storm exposures reduced birth weights and gestation lengths while increasing the likelihood of preterm and low birth weight outcomes. We also provide the first evidence that uncertain hurricane forecasts lead to individual-level disruptions in healthcare services. These impacts on birth outcomes are similar in magnitude to those found in response to other traumatic events experienced during pregnancy, such as nearby terrorist attacks36, bereavement12 and financial hardship37. A key distinction is that the driving mechanism of exposure is a public warning system that is designed to mitigate rather than exacerbate the impacts of storm events on threatened populations. Studies such as ours are a first step to timing the optimal dissemination of disaster forecasts.The evidence presented in this work is consistent with the notion that in utero tropical storm exposures create abnormal birth conditions38, show that low birth weight children weighing less than 2500 g were more than 25% less likely to pass high school English and math exit examinations and were also less likely to be employed at the age of 33. In our work, we show that in utero exposure to Hurricane Irene created a 2.52–10.34% increase in the likelihood of crossing this critical low birth weight threshold, which is increased further by storm exposure anticipation. For our birth weight outcomes, we find general effects that range from 0.17 to 0.61% and increase similarly with storm exposure anticipation. For the average individual in our lightly exposed sample (Rain ≤ 1 in), direct effects of storm exposure and indirect effects from storm forecast-driven anticipation (on average 6.5 6-h windows within the Cone of Uncertainty), cumulative birth weight reductions are approximately 1–2%. The clinical impacts of these birth weight reductions are uncertain. However, the measured magnitude is well below the commonly cited “10% change" where disruption to later life outcomes, such as high school graduation rates, IQ, income and height have been documented39.The presented findings are clinically relevant in addition to being statistically robust. Relying on British National Child Development Survey dataFindings highlight the importance of understanding risk preferences of disaster-threatened populations and institutions. In the case of Hurricane Irene, the early release of the storm track forecast is likely to have triggered a precautionary response by patients and healthcare providers. The apparent decision to cancel healthcare appointments may be driven by risk averse preferences among these groups. However, the spatial extent of those cancellations was determined by the amount of forecast uncertainty. As such, it appears that this combination of risk averse preferences and forecast uncertainty during Hurricane Irene may have disproportionately harmed the unborn. On the margin, delaying the release of Hurricane Irene’s storm forecast release may have improved birth outcomes  for 2.5 women relative to each women for which the delay would have impaired birth outcomes (increased preterm births). Evaluating the impact of storm forecast uncertainty in this way has the potential to guide cost-benefit analyses for the research and development of improved storm prediction models. Before such approaches could be used in a useful way, further study is needed to understand how disaster-threatened populations might respond to delayed but higher accuracy forecasts.The findings presented herein provide direction for several areas of future research. Empirically, heterogeneity in the estimated treatment effects should be explored to support future policy implications. Hurricane “experience" may mediate observed healthcare disruptions, which could be investigated by linking residential addresses with historical storm events and real estate records. Trimester of exposure should also be investigated to identify populations that are most vulnerable to disruptions in healthcare services and to formally validate whether prenatal care disruptions were the force driving observed birth outcomes. Behaviorally, our analysis is unable to predict the psychological impacts of a delayed storm forecast. The ambiguity (rather than uncertainty) surrounding a low-information scenario may trigger similar precautionary responses by individuals and institutions during the anticipation phase of delayed official storm forecasts. Here, future research should examine how public risk responses are likely to differ in disaster scenarios characterized by extreme ambiguity and the extent to which birth impacts from storm events are driven by physiological stress channels compared to institutional responses to situational stress. Although the analyzed data set includes all officially recorded births in North Carolina for the period 2006–2012, the study focuses on the impacts of Hurricane Irene, which may not be generalizable to other storm events that were more or less predictable and had different compositions of physical exposures . Better understanding these mechanisms that underlie population responses and institutional responses to disasters is essential to guiding future policies that might affect disaster preparedness.This study complies with ethical regulations for research on human subjects. The study is governed by East Carolina University’s IRB 17-000354 and the written informed consents for all the data were waived by the IRB. Our analysis was based on the North Carolina Department of Health and Human Services (NCDHHS) vital statistics data set for all North Carolina live and still births from August 26, 2006 to June 14, 2012. The study followed Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for reporting observational studies. We constructed a data set of 710,186 North Carolina birth outcomes with associated prenatal care and medical risk factor information that were georeferenced at the residential address level. Birth outcomes included birth weight (g) and gestation length (weeks) variables that were used to create binary indicators for low birth weight (<2500 g), very low birth weight (<1500 g), preterm (<37 weeks) and extreme preterm (<34 weeks) outcomes. Associated prenatal care indicators included the number of prenatal care visits and the gestational month in which prenatal care began. Medical risk factors included indicators for prepregnancy and gestational hypertension.43 and seasonal trends47. An annual time trend was also included to control for background trends in birth outcomes from 2006 to 2012. In all analyses, standard errors were clustered at the county level, which was the level of public health services and data collection throughout North Carolina. Clustering at the county level allowed for arbitrary serial correlation across births within the same county over time.We focused on the North Carolina impacts of Hurricane Irene, which made landfall August 27, 2011. Births that occurred in the 5 years prior to the hurricane’s impact served as a baseline of comparison against births experiencing in utero exposure to Hurricane Irene. Incorporating zip code and monthly fixed effects ensured that our estimation procedure isolated the impact of hurricane exposure on birth outcomes rather than local, social, and institutional factorsPre-hurricane births served as a control group for post-hurricane births. Constructing the data set in this way exploited the fact that prenatal, but not postnatal, exposure to a disaster may influence birth outcomes. Our empirical strategy hinged on the assumption that pregnant women did not select into treatment. We presented layers of evidence that this assumption was reasonable and that our results gleaned insight into the causal nature of in utero exposure to hurricanes on birth outcomes. Precise birth dates and residential addresses allowed us to control for local neighborhood and seasonality effects that were known to otherwise influence birth outcomes. We then used variation in a woman’s residential location relative to the NHC’s ex ante “Cone of Uncertainty" forecasts and the hurricane’s ex post storm track and associated rainfall intensities. We focused on the effects of in utero exposure to disaster stress by identifying women who were likely to anticipate direct hurricane impact but were not necessarily exposed to severe weather because of the storm’s changing trajectory.The selection of births included each woman’s expected delivery date, which was defined as 280 days after the clinically estimated date of conception. An expected delivery date within 5 years leading up to the Hurricane Irene disaster declaration date, August 25, 2011, was placed into the control group and an expected birth date within the 280 days following Hurricane Irene was placed into the treatment group. Constructing the sample in this way included all births that experience prenatal or postnatal exposure to Hurricane Irene within the relevant time window.48 and helped overcome two empirical challenges. First, opting to define the treatment window based on actual birth dates would have created a mechanical correlation between gestation length and the likelihood that a pregnant woman experienced a hurricane, i.e., longer gestation lengths led to heavier birth weights and an increased likelihood that hurricane exposure occurred during the pregnancy. Second, a large literature and our findings suggested exposure to a disaster influences gestation length. Defining the treatment window based on expected birth dates, rather than actual birth dates, ensured that the treatment window was predetermined at the time of Hurricane Irene’s arrival, i.e., there was no selection of women into treatment from exposure48.Construction of the data set followed convention in the literaturec). We defined the child’s expected birth date as eb = c + 280. The control group contained all women whose births were within x days of Hurricane Irene. We included a full 5 years, x = 1825, of control group expected birth dates to ensure that we were able to account fully for seasonality effects in birth outcomes.Formally, the sample selection contained a treatment group and a control group. The treatment group was all pregnant women residing in North Carolina during Hurricane Irene’s disaster declaration date and within the first 40 weeks following their approximate date of conception  decimal degree coordinate using the Aeronautical Reconnaissance Coverage Geographic Information System (ArcGIS) geocoder application programming interface (API) for Python (1.5.2). The coordinates were then converted into georeferenced points and used to calculate the distance of each residential location to the nearest point along a dissolved version of NOAA’s preliminary best track from the National Hurricane Center’s Geographic Information System (GIS) Archive – “Tropical Cyclone Best Track". Distance calculations were conducted using the UTM zone 17N projection. NOAA’s NHC GIS sources were also used to overlay Hurricane Irene’s “Cone of Uncertainty" predictions from advisory #7, which occurred on August 22, 2011 at 9:00 am and represented the first time that the Hurricane Irene 5-day cone approached the border of North Carolina, to advisory number #30A, which occurred on August 27, 2011 at 11:00 pm and represented the final intersection of North Carolina and Hurricane Irene’s 5-day “Cone of Uncertainty"  were diagnosed as a medical risk factor.22, we hypothesized that hurricane exposures led to reduced birth weights and gestation lengths and an increased likelihood of a preterm and low birth weight outcomes. Rainfall at each residential address was used as an indicator of exposure intensity represented by the one-day maximum rainfall from August 14, 2011 to September 4, 2011, which encompassed the hurricane event’s impact on North Carolina. Rainfall data were from the Parameter-elevation Regressions on Independent Slopes Model (PRISM) climate group Time Series Values for Individual Locations. For the control group, rainfall data from Hurricane Irene were similarly overlaid with residential addresses as if these residences experienced physical exposures. However, our selection into treatment criteria ensured that only those women within our treatment group experienced uterine exposure whereas postnatal exposure in our control group cannot impact uterine conditions or birth outcomes of infants that were born before the hurricane’s arrival. Conditioning on rainfall intensity in this way enabled a comparison of women in the treatment and control groups who presumably shared similar socioeconomic and demographic characteristics because they resided in the regions that would have been similarly exposed to Hurricane Irene’s physical impacts.Consistent with prior worki who resided in zip code z whose birth took place in month m of year y. The variable Eiymz was a binary variable that takes the value of 1 if her birth was in the treatment group and 0 otherwise. That is, μm and ζz were month and zip code fixed effects. The variable Year was a linear year trend. The dependent variable, yiymz was the birth outcome of each woman. Our estimating equation resembled12 but included an exposure intensity variable that was interacted with the treatment group binary variable. Mediating the intensity of exposure in this way allowed us to estimate non-linear impacts of hurricane exposure, across rainfall intensity, on North Carolina’s birth outcomes. Standard errors for all regressions were clustered across the State of North Carolina’s 100 counties, which was the level of public health services and data collection throughout North Carolina. Clustering at the county level allowed for arbitrary serial correlation across births within the same county over time.To measure the impact of hurricane exposures, we compared birth outcomes among two groups of women who lived in the same zip codes and experienced antenatal or postnatal exposures. The comparison groups included a “treatment” group of exposed women whose births may have been affected through in utero exposures to the physical impacts of Hurricane Irene and a “control” group of exposed women whose birth outcomes predated the hurricane’s arrival and could not have been impacted by its physical impacts. To refine our comparison groups, high-resolution rainfall intensities were predicted at each woman’s residential address and implemented as our proxy exposure variable. While unlikely within any given zip code, if Hurricane Irene’s physical exposures were systematically correlated with neighborhoods that were underserved in other ways that might impact birth outcomes , conditioning on Hurricane Irene’s rainfall intensities ensured that our treatment and control groups mirrored one another. More specifically, we estimated the following equation:ψ, as a function of RiymzWe first estimated the average treatment effect of hurricane exposure on birth outcomes and then calculated the predicted birth outcomes for each woman in our sample based on their actual exposure. More specifically, after Equation 1) was estimated, we calculated the predicted impact on an individual woman’s birth outcome,  was estiTo better understand the connection between hurricane anticipation and observed birth impacts, we overlaid the National Hurricane Center’s “Cone of Uncertainty" forecasts for Hurricane Irene with the residential addresses of all pregnant women within our sample. The spatial extent of the Cone of Uncertainty represents a zone that will contain the “eye" of an impending hurricane with approximately 66% confidence. Variation in hurricane anticipation is given by the total hours that each residential address within our sample spends within this cone Fig. . The conWe stratified our sample into three categories that experienced light rainfall (<1 inch of rain within the most intensive 24-h period), moderate rainfall (1–2 inches of rain within the most intensive 24-h period) and heavy rainfall (>2 inches of rain within the most intensive 24-h period) during Hurricane Irene. Following the same empirical approach as previous analyses, our baseline group of comparison represented births from residential addresses that would have experienced the same light, moderate and heavy rainfall conditions if their pregnancies had overlapped with Hurricane Irene, i.e., births occurred in the same location but at a slightly later time. Separating the sample into categories of physical exposure allowed us to measure the additional benefit (or harm) that resulted from advanced warning that signaled potential impact ahead of a storm event that ended up bringing either mild, moderate or severe weather.In other words, our approach isolated both (i) the reproductive health benefits of an advanced warning system that avoids a type II forecasting error—i.e., correctly provides additional warning time to vulnerable populations that received intense physical exposures—and the reproductive health harm of an advanced warning system that committed a type I forecasting error, i.e., incorrectly provided additional warning to vulnerable populations that only received mild physical exposures. In such a latter case, additional exposure anticipation may lead to the (ex post unnecessary) cancellation of prenatal care appointments, which may inadvertently cause harm to birth outcomes.Eiymz was the treatment binary variable and yiymz was the birth outcome. The variable Ciymz was the number of 6-h advisories for which a woman’s residence was within Hurricane Irene’s cone of uncertainty. Such variation in advisories revealed the intensity of type I errors for those locations that experienced only mild weather exposures. The coefficient β4 was the marginal effect of an additional advisory at the residence of an individual in the treatment group. While no advisories occurred for women in the control group, we calculated these advisories using the same approach to ensure that geographic factors were fully controlled. This approach, and interacting our advisory variable with our exposure indicator, ensured that our estimated marginal effects were unique to exposed women, not driven by other geographic factors local to where advisories were issued.To examine the effect of hurricane anticipation  on birth outcomes, we augmented the estimating equation as follows:Further information on research design is available in the Supplementary InformationReporting SummaryPeer Review File


The association between medically assisted reproduction and pregnancy planning on overall developmental outcomes of infants has been studied in relatively few studies. The availability of accurate tools for the early detection of developmental delays is a major issue. The purpose of this study is describing the average neurodevelopment of preterm infants and assessing the association between medically assisted reproduction, pregnancy planning and neurodevelopmental outcomes among Hungarian preterm infants.N = 171) who underwent developmental assessment using Bayley-III Screening Test  in five developmental domains  at 12 months of corrected age. We examined the developmental pattern of infants and the potential associations between medically assisted reproduction, pregnancy planning and Bayley-III Screening Test subscales. Information on the mode of conception and pregnancy planning was obtained through parental anamnesis.Cross-sectional study of preterm infants with gestational age < 37 weeks (Concerning the risk for developmental delay, the language and motor subscales were the most affected. Examination of the mode of conception and developmental outcomes revealed higher neurodevelopmental skills in infants who were conceived through medically assisted reproduction. Significantly lower cognitive, receptive and expressive language skills were found to be associated with unplanned pregnancies. Multi-way analysis of variance was conducted in order to assess the impact of the mode of conception and pregnancy planning on subscales.We cannot unambiguously conclude that MAR and pregnancy planning had a solely positive effect on the development of preterm infants at 12 months of corrected age, but our results are vital for the design and implementation of further research. In spite of the development of medical sciences, the number of preterm births is increasing worldwide. Every year approximately 15 million babies are born preterm (before 37 weeks of pregnancy); often associated with an overlapping perinatal risk, low birth weight < 2500 g). Preterm birth is not only the leading cause of death among children under the age of 5 500 g. Pr.The presence of neonatal morbidities like bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), chronic lung disease (CLD), and sepsis may associate with lower neurodevelopmental outcomes –7. BPD, Higher preterm birth rates and lower birth weight can often be identified in unplanned and children conceived through assisted reproduction , 22. NexTo resolve the problem of infertility and involuntary childlessness, assisted reproductive technologies offer a set of techniques (among others e.g. intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), frozen embryo transfers) , 24. HowPregnancy planning is generally related to prenatal and postnatal behaviour of parents . AccordiDescription of the neurodevelopmental outcomes  of preterm infants at 12 months of corrected age in a Hungarian sample.Examination of the potential association between medically assisted reproduction, pregnancy planning and neurodevelopmental outcomes of preterm infants at 12 months of corrected age in a Hungarian sample.The objective of this study:Pediatric Psychology and Psychosomatic Unit of the Department of Pediatrics of the University of Debrecen between December 2017 and May 2019. In our sample the main inclusion criteria was the prematurity and the undergoing of all the five subscales of Bayley-III Screening Test. Note that, everyone in the sample happened to have LBW, though it was not an inclusion criteria. Every subject who was born prematurely at the Department of Obstetrics and Gynecology of the University of Debrecen between December 2016 and May 2018 (N = 640) was invited to take part in the examination, except for infants with severe damage and those how have died. A total of 469 subjects were excluded  from the examinations. 169 infants from our sample were delivered in the same maternity ward, at the Department of Obstetrics and Gynecology of the University of Debrecen, while there were only two who were outborn . Our sample covers all available cases in the Eastern region of Hungary. Correction for prematurity was made based on the instructions of the Screening Test Manual [In this work 171 preterm (< 37 weeks) infants at 12 months of corrected age were examined at the t Manual . The stuDevelopmental psychodiagnostic tools play an important role in the identification of developmental delays. BSID-III  – the advanced version of BSID-II  – is currently the most advanced and widespread developmental tool for infants and toddlers . Due to Department of Pediatrics of the University of Debrecen. Information about the mode of conception ) and pregnancy planning (planned – unplanned) was obtained based on a maternal anamnesis.Developmental characteristics , were obtained from the clinical database of the IBM SPSS Statistics v25 was used.Several descriptive statistics were calculated for infants’ main characteristics  and developmental performance. Independent-samples (Student’s) t-test was used to compare the means of neurodevelopment of infants conceived by MAR or naturally and planned or unplanned infants. If the standard deviations of the compared populations did not coincide, Welch’s t-test was used, instead, as the natural alternative test. In addition, a non-parametric alternative, the Mann–Whitney test, was also carried out to analyse the difference in the distributions of the compared groups for the key variables . Note that, the latter one is fairly useful in case of smaller sample size. Comparison of the distribution of some nominal variables  again between MAR and naturally conceived as well as planned and unplanned groups were done by χ^2 test. To examine whether mode of conception and pregnancy planning were the most influencing factors for positive or negative changes in cognitive, language (receptive and expressive) and motor (fine and gross) development, analysis of variance (ANOVA) was performed with several factors (‘multi-way’) including possible interactions as well. We tested whether the independent variables in neurodevelopmental outcomes remain significant or not, in addition to other explanatory factors. For all statistical analysis, n = 171) were Hungarian and had valid health insurance. The gender ratio was close to equal, 83 females and 88 males were examined. The mean birth weight of infants was between 260 and 2490 g . Gestational age of our sample was also low . Main characteristics of our entire sample are shown in Table In what follows, notations M, SD and n are used for sample mean, sample standard deviation and sample size, respectively. All infants participating in the study n = 71 were HOne of the great benefits of the Bayley-III Screening Test is its ability to predict the risk of developmental delays. It can distinguish high, moderate and low risk for developmental delays compared to levels expected based on their age. In our sample, the proportion of 'high risk for developmental delay' was low, ranging from 0%  to 2.92% . The proportion of ‘moderate risk for developmental delay' was slightly higher, ranging from 11.11%  to 27.48%  (Table n = 2), artificial insemination (n = 6) and IVF (n = 24) occurred, so we formed an integrated MAR group. At the level of descriptive statistics (mean ± std. dev.), MAR group  had higher mean values than naturally conceived peers  at the birthweight and gestational age. Examining the Bayley-III Screening Test scores, in the group of infants conceived through MAR and naturally, we found that the neurodevelopment of infants conceived by MAR was above average in all developmental areas compared to naturally conceived peers (Table p < 0.05) were found at receptive language and gross motor subscales on both t-tests and Mann–Whitney tests.In our sample 47 (27.48%) children were conceived through medically assisted reproduction with 124 (72.51%) infants conceived naturally, without any medical assistance. In 15 cases we did not get any information about the special type of medically assisted reproduction, only ovulation induction (p < 0.05) differences in birthweight, 1 min and 5 min Apgar scores, maternal age, maternal education, marital and social status. Infants conceived by MAR had higher Apgar-scores and their mothers were older in average. Having a look at the percentage relative frequency distribution, we found higher proportions in case of LBW and VLBW infants in the MAR group, whereas mothers in the MAR group had a lower incidence of low and secondary education and a higher incidence of college and university education. Furthermore, proportions of marriage, cohabiting as well as the above-average social status are higher than in the group of naturally conceived peers  were intended pregnancies. We identified unplanned pregnancies in 17 cases (9.94%) and we did not get any information about pregnancy planning in 5 cases (2.92%). Examining the mean birth weight and gestational age of planned  and unplanned  infants we identified higher birth weight in the planned group. Examining the subscales of Bayley Screening Test, planned infants showed higher scores for all variables. The Mann–Whitney test showed significant differences (p < 0.05) between planned and unplanned pregnancies on cognitive, receptive and expressive language subscales. T-tests showed similar results, significant differences were identified on the cognitive, receptive language and gross motor subscale levels  differences in maternal age and marital status. Mothers in the unplanned group were younger in average; analysing the percentage relative frequencies one can see that single marital status was higher, while marriage was lower than in the planned group. Note further that the percentage relative frequency distributions seem to be different in the planned and unplanned groups e.g. in case of the variables birth weight and maternal education, that is the proportions of VLBW and ELBW infants, the low and secondary education are all higher in the unplanned group, but presumably there is no significant difference due to the small sample size  and One-Way ANOVA and with their non-parametric counterparts, Mann–Whitney and Kruskal–Wallis tests. For some variables, where there were appropriate scales, the relationship was tested with the existence of a significant correlation. In case of marital status, maternal education, housing, social status, and income variables no significant relationship was identified using the Bayley-III Screening Test subscales, so these variables were excluded from further analyses. Five independent variables (factors)  were considered, which we hypothesized they may influence – at least or have relationship with – the neurodevelopmental variables. These five variables were our explanatory factors in ANOVA, such that interactions were also included in the model. It would be interesting to extend our analysis with further determinants, such as BPD, IVH, NEC, or ROP. However, one can see the very low frequency values for the positive cases of these neonatal morbidities in the sample (see Table p = 0.002). For the expressive language subscale, MAR showed a weak, but significant relationship  as it can be detected only with a first-order error (p < 0.01). Interaction of gestational age with the MAR variable had an explanatory power on the expressive language subscale . Concerning the gross motor subscale, birth weight  and pregnancy planning  variables had an independent and joint impact . The mean neurodevelopmental performance of each group is shown in Tables According to the results of ANOVA, no significant relationship could be identified on the cognitive or fine motor subscales in case of the five factors. Concerning the receptive language subscale, the pregnancy planning variable had a significant role  than naturally conceived children. According to the results of the ANOVA technique, the mode of conception had an independent role on the expressive language subscale, and we also found explanatory power in interaction with gestational age. We can assume that these children may have experienced greater parental attention and care from the moment of conception; factors that may have contributed to higher cognitive, language and motor development at 12 months of corrected age. Based on the literature findings parents may perceive their infants more fragile due to the health outcomes (e.g. increased risk of preterm birth and LBW), the long conception procedure, so they pay more attention and care of them, which can be reflected in higher neurodevelopmental outcomes in the early years of life. The financial and emotional efforts to have a baby conceived by MAR can also contribute to the higher care in parenting , 58.Review of studies about pregnancy planning shows that there is relatively scarce international research where long-term developmental pathways are followed. This line of our research is considered completely groundbreaking in Hungary. Many factors can adversely affect the development of a child born from an unplanned/unintended pregnancy . Carson Our results show significantly lower language skills already at 12 months of corrected age, as well as significantly lower cognitive skills. With ANOVA, we examined whether differences in neurodevelopmental performance can be explained by pregnancy planning. In the cognitive subscale, pregnancy planning was not considered significant. In case of the receptive language subscale, pregnancy planning had an independent impact on performance, while in the gross motor subscale birth weight and pregnancy planning had both an independent and interactive role on the subscale. Although we can identify higher mean scores of planned infants, it cannot be concluded that pregnancy planning is solely responsible for all differences. However, it must be emphasized that pregnancy planning alone had a significant role on receptive language and gross motor subscales.Potential limitations of our study are the small sample size in certain groups; however, our sample covers all available cases in the Eastern region of Hungary. Other limitations are the absence of a full-term control group, and the fact the emotions related to conception and time from pregnancy planning to conception were not measured. To overcome these limitations we examine our sample’s development with the full BSID-III assessment at the 24 months of corrected age, ask more detailed information about the circumstances of pregnancy planning and gather an adjusted full-term control group.With our statistical analysis, we cannot unequivocally conclude that MAR and pregnancy planning had the main role on the neurodevelopment of preterm infants at 12 months of corrected age, we can only determine a positive association between variables by the statistical tests, and not necessarily a causal relationship. Though we note again that some (socio-demographic) variables explaining partially the parental characteristic was included in the analysis but have been found not to have any significant explanatory power when we took into account the role of other factors (see ANOVA results) jointly.In terms of neurodevelopmental and intellectual development, preterm children can be regarded as a vulnerable population , 45. Unp


Although the percentage of cesarean sections (CS) in Czechia is below the average of that of other developed countries (23.6%), it still exceeds WHO recommendations (15%). The first aim of the study is to examine the association between a CS birth and the main health factors and sociodemographic characteristics involved, while the second aim is to examine recent trends in the CS rate in Czechia. Anonymized data on all mothers in Czechia for 2018 taken from the National Register of Expectant Mothers was employed. The risk of cesarean delivery for the observed factors was tested via the construction of a binary logistic regression model that allowed for adjustments for all the other covariates in the model.p<0.001). The breech position increased the risk of CS by 31 times . A multiple pregnancy increased the odds of CS six-fold and the use of ART 1.8-fold. Mothers who suffered from diabetes before pregnancy were found to be twice as likely to give birth via CS , while mothers with gestational diabetes had just 23% higher odds of a CS birth . Mothers who suffered from hypertension gave birth via CS twice as often as did mothers without such complications .Despite all the covariates being found to be statistically significant, it was determined that health factors represented a higher risk of a CS than sociodemographic characteristics. A previous CS was found to increase the risk of its recurrence by 33 times (OR = 32.96, 95% CI 30.95–35.11, The increasing age of mothers, a significant risk factor for a CS, was found to be independent of other health factors. Accordingly, delayed childbearing is thought to be associated with the increase in the CS rate in Czechia. However, since other factors come into play, further research is needed to assess whether the recent slight decline in the CS rate is not merely a temporal trend. Cesarean section (CS), when used appropriately, should account for 10–15% of births . In receOne of the most likely reasons for this phenomenon concerns the dynamic increase in the age of mothers , which rThe reasons for the increase in the CS are multifactorial and include health care practices , 3. The The first aim of the article is to evaluate, taking Czechia as an example, the association between the use of CS and the main medical factors related to the increased use of CS  and to subsequently compare these associations with those between the use of CS and sociodemographic characteristics . The second aim is to examine recent trends in the CS rate in Czechia.The study employed a unique data source that contains anonymized data on all mothers in Czechia for 2018 obtained from the National Registry of Mothers at Childbirth (NRMC), which is managed by the Institute of Health Information and Statistics of the Czech Republic (IHIS CR) . The datIn 2018, a total of 111,749 mothers gave birth to 113,234 children; 6.2% of them had non-Czech citizenship [Firstly, a descriptive analysis of the relationships between the observed variables was conducted so as to evaluate the distribution of the increased incidence of CS births according to the various factors considered. Most of the monitored variables contained data on all the mothers, with the exception of marital status and level of education; the completion of these questions is optional. There was a lack of information on 673 mothers concerning marital status  and on 23,113 mothers in the case of the level of education . Cesarean deliveries were divided into planned and acute.In order to assess the association between the various covariates and the risk of CS, a binary logistic regression model was constructed, which enabled the testing of the association of the various variables on the incidence of CS births , assuming all the other characteristics of the mothers were equal. The application of the binary logistic regression model allowed for the removal of the mutual influence of the covariates and the testing of whether they also acted individually, all else being equal.N = 88,041, i.e. 79% of the total number of mothers), while Model 2 included only those mothers who had already given birth in the past .Two logistic regression models were constructed. Model 1 included all the mothers except for those for whom no data was available on the marital status and level of education ’ is the vector of the explanatory variables:The binary logistic regression model was used to explain the effects of the explanatory variables on the dependent variable “having a childbirth via cesarean section” . 0 is the intercept parameter and β is the vector of the slope parameters.where βFor the sake of clarity, the results were interpreted in terms of odds ratios (OR), which qualify the variables that indicate the odds of cesarean delivery for each category compared to the given reference category.Marital status was divided into four categories: single, married (ref.), divorced and widowed.level of education was divided into four groups: basic (including incomplete), secondary without the school leaving certificate (SLC), secondary with the SLC (ref.) and tertiary.The highest attained The WHO classification of premature babies  was usedbirth order was divided into 3 categories, namely women who had not yet given birth (ref.), women who had given birth for a second time, and women with third and higher order births.The Singleton (ref.) versus multiple pregnancy.Previous CS birth : no (ref.), yes.probable method of pregnancy of the women was estimated based on the embryo transfer date reported for 4,018 mothers. This method of assisted reproduction was used by 3.6% of mothers. This variable was then divided into two categories – without the use of ART (ref.) and following ART.The incidence of diabetes in the mothers was divided into three categories: not detected (ref.), detected prior to pregnancy, detected during pregnancy.The serious complications during pregnancy and childbirth. Other complications  were combined in the “other complications” category.Hypertension and threatened preterm labor, which are among the most common health complications, were identified as The models also considered the incidence of a breech presentation. This variable was assigned the values: no (ref.) and yes. In the case of multiple pregnancies, the pregnancy was classified as “yes” if at least one of the children was in the breech position.A number of demographic, health and socio-economic characteristics were included in the models as explanatory variables. With the exception of the age of the mother at childbirth (continuous), all the following covariates were categorical and were transformed into dummy variables:birth weight was not included in the regression model since it is not considered to be a key indicator of CS. The preferred routine adopted by the field of obstetrics in Czechia comprises the evaluation of placental functioning applying the ultrasonographic measurement of flow through the umbilical artery and the middle cerebral artery. The birth weight is recorded only following the birth of the child; data on the estimated birth weight of the child prior to the birth does not form a part of the official data on which a decision on a CS is based.The In addition, the variable birth weight, which has a high degree of multicollinearity with the gestational age, was monitored in the descriptive analysis via the following 5 categories: extremely low birth weight , very low birth weight , low birth weight , normal birth weight  and high birth weight  . The anaThe analysis was performed using SPSS Statistics 26 software. The findings and the discussion are reported according to STROBE Statement guidelines .In 2018, a total of 111,749 mothers gave birth to 113,234 children in Czechia [In 2018, 6.9% of mothers gave birth prematurely in Czechia and 48.2% of all mothers gave birth to their first child. 35.3% of mothers had second-order births and the remaining 16.5% had third-order and higher births. 10.5% of mothers had experienced at least one previous CS birth. 1,464 sets of twins were born in Czechia in 2018, i.e. 1.3% of all births.The share of CS births in 2018 was 23.6%. The highest proportion of CS births concerned elective CS planned during pregnancy (42.9%) and, together with elective CS, but performed during labour (7.8%), accounted for a total of 50.7%. Emergent cesarean sections performed during labor accounted for 33.5%, and during pregnancy 15.8%. Of all women who gave birth via CS  62% were aged 30 and over. 31.8% of all CS births were repeat CS births, of which 18.9% were breech presentations, 6.4% followed ART and 4.4% were multiple pregnancies.The distribution of CS according to age categories indicated an increasing risk with the age of the mother Table . The lowIn addition, the ratio of planned and emergent CS also varied depending on the age of the mother Fig. , i.e. thThe proportion of CS births varied slightly depending on the birth order Fig. . The higSignificant differences were determined with respect to the number of pregnancies and whether or not the mother had previously given birth via CS Table . MultiplThe proportion of CS births increased in proportion to the occurrence of complications during pregnancy and childbirth Fig. . The risThe incidence of various types of complications during pregnancy and childbirth also varied depending on the age of the mother. Complications such as first and third trimester bleeding, placenta previa, placental abruption and other placental abnormalities, cardiovascular complications and hypertension primarily affected mothers over 35 years of age, and even more significantly mothers over 40 years of age. Conversely, some complications were characteristic of younger mothers under 24 years of age, specifically the occurrence of a significantly higher proportion of the threat of pre-term birth and intra-uterine growth restriction. The incidence of other health complications  did not differ significantly according to the age of the mother.However, the proportion of diabetes, especially diabetes that was detected during pregnancy, increased with the age of the mothers Table ; while 6CS delivery was observed to be less frequent for women who became pregnant without ART (22.9%) than those who underwent assisted reproduction techniques (42.2%) Fig. .Of all children born via CS, 18.6% were in the breech presentation, 3% in the transverse and oblique lie and 78.4% were in the vertex presentation. Only 9.8% of children in the breech presentation were born spontaneously.The proportion of CS births varied significantly according to the birth weight of the child Fig. . CS was The final observed change concerned the gestational age. Significant differences were observed between mothers of gestational ages ranging from 22 to 45 weeks. The proportion of CS was significantly higher for pre-term births than for term births, while the share was slightly higher for post-term births Fig. . ExtremeThe sociodemographic characteristics and health status of all the women were analyzed together employing binary logistic regression in order to identify the covariates associated with the increased odds of a CS delivery. All the covariates were entered into Model 1 for 88,041 mothers .The results revealed that the odds of a cesarean birth increases with the maternal age (Table p<0.001) and 25% lower for mothers of higher order births . Women who gave birth to multiple children had 6-times higher odds of a CS  than women with singleton pregnancies. Slightly higher odds of a CS birth were detected for single women  than for married women. No significant difference was observed with respect to the other categories. In terms of the level of education attained, lower odds of giving birth via CS were detected for women with a tertiary education  compared to women with secondary education with SLC.The odds of a CS decreased with the birth order: for second-time mothers the odds were 11% lower than for first-time mothers . Women who gave birth pre-term also had higher odds of giving birth via CS, especially those who had very pre-term births . Further, women who most likely became pregnant following embryo transfer had significantly higher odds of a cesarean delivery, even after adjusting for the mother’s age and the birth order and frequency; the odds of giving birth via CS were 1.8-times higher than for women who did not undergo ART . Mothers who suffered from diabetes prior to pregnancy were more than twice as likely to give birth via CS than women who did not have the condition , while those with gestational diabetes had only 1.2-times higher odds . Furthermore, mothers who suffered from hypertension had twice the odds of a CS birth than those without such complications .In terms of health characteristics, the breech position comprises a decisive indication for a CS birth; the odds of a CS birth were more than 30 times higher than for women whose child was in a different position . Either no change was observed with respect to the association of the other monitored variables  or the odds even increased . The odds of CS for women who gave birth very pre-term was 3.5-times higher  than for those who gave birth within term, and the odds of CS for women with a multiple pregnancy was almost 9-times higher  than for those who had a singleton pregnancy.Model 2 included only those women who had already given birth , which allowed for the addition of the very significant variable of whether the woman had given birth via cesarean section in the past  . HoweverA further reason for the increase in CS births concerns the move away from spontaneous delivery when the fetus is in the breech presentation. This trend, initiated by the Term Breech Trial Collaborative Group study , has graThe literature shows that a number of maternal health risks are age-related and that the risk of a cesarean birth increases with the maternal age , 40, 41.P < 0.001). A recent Danish study [P < 0.001).Furthermore, our results confirmed the age factor as an independent risk for CS birth. Similar results were reported in a British study , the samsh study  showed tThus, one of today’s most important population trends – fertility postponement – also comprises one of the significant independent factors associated with the risk of a CS birth. According to Timofeev et al. , the ideThe highest fertility rate in Czechia in 2018 was attained by women aged 30, in contrast to the early 1990s when maximum fertility was attained at the age of 22 . The shiA further risk factor that is closely connected with fertility postponement concerns the use of ART. Our results confirmed that mothers who most likely became pregnant following embryo transfer also had 1.83 higher odds of a cesarean delivery, even when controlling for the age, order and frequency of birth. According to the meta-analysis of the Medline, EMBASE and CINAHL databases , IVF/ICSIt is noteworthy that, despite the decline in marriage, marital status continues to comprise a relevant variable. In Czechia a slightly higher risk of CS (OR 1.06) was observed for single compared to married women despite the control of variables such as the age of the mother and the birth order. The higher risk of giving birth via CS for single women may be due to the fact that marital status is related to the health status, i.e. married persons have a higher level of self-esteem than do single people .With regard to the level of the woman’s education, no significant differences were detected in terms of the risk of a CS between women with a basic but incomplete education, secondary without the SLC (school leaving certificate) and secondary with the SLC. The controlling of the age and other variables revealed lower odds of a CS birth (OR 0.89) for tertiary-educated women than those with the SLC. The higher odds of CS for women with lower levels of education could be explained by their working in riskier professions, a higher incidence of smoking or obesity or generally poorer living conditions . ConversThe trend toward an increase in CS in Czechia can also be understood from the legislation perspective, in particular with concern to the introduction of the new Civil Code in 2014, which replaced clearly-defined compensation levels for personal injury with the decision on the amount thereof being decided solely by the courts. The courts continue to maintain the misconception that CS is the best form of intervention in terms of assuring the health of the child and mother. A similar situation has been reported by Longo with respect to Italy , 60, 61.The share of CS births in Czechia (23.6%) exceeds WHO recommendations of 2015 on the optimal proportion of CS births (10–15%). Based on our results, we doubt whether the WHO recommendations reflect the increasingly older ages of mothers, especially first-time mothers and the high degree of institutionalization of deliveries in developed countries. Trusting the delivery to physicians is usually accompanied by a significantly higher degree of monitoring, with the associated risks of false-positive indications of hypoxia, a higher rate of medication use, and the loss of faith in normal childbirth .Some women prefer a CS since they consider it to be safer for both themselves and the baby, an opinion that runs contrary to current scientific knowledge. A history of CS is associated with a higher risk of uterus rupture, placenta accreta, ectopic pregnancy, stillbirth, pre-term birth, and bleeding and the need for a blood transfusion, injury during surgery and hysterectomy in subsequent pregnancies. A higher birth order CS also increases the risk of maternal mortality and morbidity compared to a vaginal delivery .CS may also lead to enhanced health risks for the baby – altered immune development, the increased likelihood of allergies, atopy, asthma, a reduction in intestinal microbiome diversity  and lateThus, it is important that all the indications concerning birth via CS are carefully considered and that this method is not overused. Czechia makes no effort to contribute to efforts to reduce the percentage of cesarean sections; on the contrary, the reimbursement of costs by health insurance companies is higher for a cesarean section than for a spontaneous birth. One of the measures that might significantly prevent the expansion of CS use concerns a recommendation from the relevant professional authorities to strictly refuse cesarean sections on request . AlthougIn conclusion, despite the international concern surrounding the increasing CS rate, the Czech CS rate decreased from 26.1% in 2015 to 23.6% in 2018. Interestingly, this has not been attributed to any particular Czech health strategy aimed at reducing the CS rate. Although it has been perceived as a significant success for the field of Czech obstetrics, further research is needed in order to assess whether this is not merely a temporal trend.Delayed childbearing appears to be associated with the increasing use of CS in parallel with the expansion of defensive obstetrics that imply a high risk of CS in cases of a breech presentation and following a previous CS. In addition, the increased use of CS also reflects social demand, an increasing trend toward the prosecution of obstetricians in the event of childbirth complications and the erroneous lay perception of CS as the safest and least painful childbirth method. On the other hand, clinical practice based on the official refusal of CS on request could well prevent the overuse of CS. As regards obstetric practice, measures to encourage TOLAC, albeit with a careful eligibility assessment, may also help to reduce CS. As regards non-clinical interventions targeted at women, the support of training programs and health education on the indications and contra-indications of CS may also serve to improve the CS rate.The aim of the study was to contribute to the explanation of recent trends in the CS rate in Czechia based on the examination of the association between a CS birth and selected health factors and sociodemographic characteristics. Our analysis confirmed that the mother’s age comprises an independent risk factor for a CS birth in addition to pregnancy health complications and other, sociodemographic, characteristics. Accordingly, delayed childbearing appears to be associated with the increase in the CS rate in Czechia. However, the recent slight decline in the CS rate may be related to the completion of the fertility postponement process in Czechia. Nevertheless, since other factors come into play, further research is required in order to assess whether the recent slight decline in the CS rate is not merely a temporal trend.


Preterm birth and subsequent neonatal ventilatory treatment disrupts development of the hypoxic ventilatory response (HVR). An attenuated HVR has been identified in preterm neonates, however it is unknown whether the attenuation persists into the second year of life. We investigated the HVR at 12–15 months corrected postnatal age and assessed predictors of a blunted HVR in those born very preterm (<32 weeks gestation).IO2) from 0.21 to 0.14. Respiratory frequency (f), tidal volume (VT), minute ventilation (VE), inspiratory time (tI), expiratory time (tE), VT/tI, tI/tTOT, VT/tTOT, area under the low-volume loop and peak tidal expiratory flow (PTEF) were measured at the first and third minute of each FIO2. The change in respiratory variables over time was assessed using a repeated measures ANOVA with Greenhouse-Geisser correction. A blunted HVR was defined as a <10% rise in VE, from normoxia. The relationship between neonatal factors and the magnitude of HVR was assessed using Spearman correlation.HVR was measured in infants born very preterm. Hypoxia was induced with a three-step reduction in their fraction of inspired oxygen (FVE) in response to decreasing FIO2 from 0.21 to 0.14. However, 17 infants (44%) failed to increase VE by ≥10% (range −14% to 9%) and were considered to have a blunted response to hypoxia. Males had a smaller HVR than females [ΔVE ].Thirty nine infants born very preterm demonstrated a mean (SD) HVR of 11.4 (10.1)% (increase in Infants surviving very preterm birth have an attenuated ventilatory response to hypoxia that persists into the second year of life, especially in males. The  , 2. The2) , 4. At be phase) . The depe phase) , 7, as we phase) . Howevere phase) . In conte phase) .The maturation of the HVR continues through infancy. Several previous studies in both preterm and term infants , 11–17 hIO2) in preterm born infants at 12–15 months corrected postnatal age. Further, we aimed to determine if the magnitude of the HVR beyond the first year of life was associated with neonatal factors, such as duration of supplemental oxygen and duration of respiratory support. We hypothesised that preterm infants would mount a HVR at 12–15 months postnatal age, but that the HVR would be blunted (defined a priori as <10% increase in minute ventilation) in those receiving prolonged oxygen therapy and/or respiratory support, during the neonatal period.We aimed to explore the hypoxic ventilatory response to a stepwise reduction in the fraction of inspired oxygen ] at King Edward Memorial Hospital with no congenital abnormality. All infants were part of the Preterm Infant Functional and Clinical Outcome (PIFCO) study, a cohort evaluating the pulmonary and cardiovascular outcomes following preterm birth (ACTRN12613001062718). Neonatal clinical information and data on respiratory support were obtained from the prospectively collected PIFCO REDCap database . Broncho2)  were measured continuously. The dynamic oxygen test was performed at the end of the infant's lung function test session, approximately 40 min after the infant fell asleep.Infants were sedated with 80 mg/kg chloral hydrate  for the duration of the infant lung function testing. The infant's level of consciousness and capillary refill time were measured every 15 min by the attending physician. Heart rate and peripheral oxyhaemoglobin saturation  to 0.19, then 0.16 and finally 0.14 oxygen in nitrogen balance, delivered at a continuous flow of 10 L/min via a sealed face mask , sampled via a port proximal to the facemask. The respiratory gases, FIO2 and SpO2 were recorded continuously and then analysed offline using Lab Chart . Each step lasted for 3 min duration, with tidal breathing measured during the first (to assess the peak acute response to the reduction in FIO2), and third minute of each FIO2 step using an ultrasonic flowmeter .. Ventilation variables, including inspiratory time (tI), expiratory time (tE), total breath duration (tTOT), time to peak tidal expiratory flow (PTEF), tidal volume (VT), respiratory rate (f), minute ventilation (VE), VT/tTOT, VT/tI, tI/tTOT and area of the flow-volume loop were determined .The change in ventilatory variables (Δ) from baseline were determined by subtracting baseline measurement from those obtained during the first and third minute of each FIO2 step.The Face mask . Equilibp < 0.05. Data analysis was performed with the use of IBM Statistical Package for the Social Science (SPSS) software .Differences in neonatal, demographic and HVR characteristics between preterm born infants with and without a diagnosis of BPD were assessed using Student's T- test or Mann-Whitney U test as appropriate for the data distribution. Change in each tidal breathing variable over time was assessed using repeated measures ANOVA with Greenhouse-Geisser correction. A blunted HVR was considered to be a <10% increase in minute ventilation. Post hoc analysis was conducted with Bonferroni adjustment. Factors associated with the magnitude of HVR were assessed using Spearman correlation. Significance was considered at An oxygen reduction test was completed in 39 infants surviving very preterm birth at a mean (SD) of 14.4 (1.0) months corrected postnatal age. Sixteen of the 39 infants were classified as having BPD. As expected, infants with BPD were more immature, had lower birthweights and required increased respiratory support compared to those infants without BPD. Demographic and neonatal information are shown in VE of 11.4 (10.7) % in response to decreasing FIO2 from 0.21 to 0.14 (VE by ≥10% (range −14% to 9%) and were considered to have a blunted response to hypoxia, compared to the responders (range 10% to 37%). Of these 17 infants, 5 had reductions in VE that was below baseline values; all were boys.Infants born very preterm demonstrated a HVR: there was a mean (SD) increase in  to 0.14 . HoweverVT, VE, VT/tTOT,VT/tI, and area of the flow volume loop differed significantly between time points during the exposure to moderate hypoxic gas mixture (p < 0.001): Each of these outcome variables increased during the first minute of exposure to 0.16 FIO2, and during both minute 1 and 3 of 0.14 FIO2, compared to baseline  during the first minute of 0.14 FIO2. Accordingly, we also observed decreased ΔtI/tTOT  and increased ΔVT/TI  in those with BPD.As the first minute of exposure to an FVE , ΔVT/tI , and ΔVT/tTOT  in response to 0.14 FIO2 compared to female infants .Several neonatal factors were associated with HVR magnitude including gestational age, duration of respiratory support, duration of oxygen therapy, and shift of the oxyhaemoglobin curve at 36 weeks postmenstrual age . The ΔHVWe report that infants born very preterm have a small ventilatory response to hypoxia at 12–15 months corrected postnatal age (mean (SD):11.4% (10.7) increase in minute ventilation), that is largely driven by an increase in tidal volume. However, the HVR was blunted (<10% increase in minute ventilation) in almost half of the infants studied. Interestingly, the magnitude of the HVR was not reduced in infants with BPD but was reduced in male infants.IO2  while others have used an instant reduction in FIO2 from baseline , when exposed to 0.15 FIO2 . In contIO2 . UnfortuIO2 , with thIO2 . Taken tbaseline , 22, ratA single small study has previously evaluated the ventilatory response to hypoxia beyond the first year of life, and reported a blunted HVR in young adults born <32 weeks gestation compared to term born young adults (receiving a 60 s hypoxic exposure), despite similar respiratory function and exercise capacity . UnfortuVE) was not different between infants with and without BPD, nor associated with NICU factors such as the duration of supplemental oxygen. However, the strategies by which the infants altered their ventilation was related to neonatal factors. For example, infants with higher duration of supplemental O2, or increased right shift of the oxyhaemoglobin dissociation curve in the NICU, showed increase in the “driving components” (VT/tI) of the breathing cycle and decreases in the “timing components” or duty cycle (tI/tTOT) during hypoxia, largely influenced by a reduced inspiratory time. Such observations may highlight ongoing alterations to central respiratory neural networks and/or respiratory system compliance in preterm infants requiring additional respiratory support in the NICU. Indeed, a short inspiratory time (tI) is common in preterm neonates, relative to term born infants, and hinders adequate ventilation and oxygenation (The ventilatory response to hypoxia (% change in genation . Furthergenation  and an agenation . It remagenation .VE falling below baseline levels in response to hypoxia were boys. Sex differences in the magnitude of the acute HVR have generally not been observed in term-born humans, once accounting for differences in body size (We showed a reduced ventilatory response to hypoxia in males born preterm. Further, all 5 infants with ody size  or baselody size . Howeverody size –39, and ody size . For exaody size –43 in thody size , brief rody size , and sleody size  is increOur infants were studied while sedated with chlroral hydrate, which likely affected sleep state. Chloral hydrate is reported as safe to use during hypoxia and has minimal effect on ventilation , 48. HowIn summary, we show that some infants surviving very preterm birth have an attenuated ventilatory response to hypoxia that persists into the second year of life, especially males. Although it is unclear why some preterm infants have a dampened HVR, these findings further our understanding that preterm infants may be at increased risk of disorders of respiratory control throughout life.


Low birth weight (LBW) and preterm birth are adverse perinatal outcomes that pose a significant risk to a child’s healthy beginning. While antenatal care (ANC) is an established intervention for pregnancy care, little is understood about how the number and timing of ANC visits can impact these adverse health outcomes. This study aimed to examine the impact of the number and timing of ANC visits on LBW and preterm birth in a regional setting. A decade-long perinatal dataset related to singleton live births that took place in the Southern New South Wales Local Health District (SNSWLHD) was utilized. The outcomes of interest were LBW and preterm birth, and the exposure variables were based on the Australian pregnancy guidelines on the number and timing of ANC visits. A multivariable logistic regression was performed to measure the association between outcome and exposure while adjusting for potential confounders. A greater level of protection against LBW and preterm birth was observed among mothers who had an adequate number of visits, with early entry (first trimester) into ANC. The protective effect of an adequate number of ANC visits against LBW and preterm birth among mothers with late entry into ANC (third trimester) was found to be statistically non-significant. Low birth weight (LBW) and preterm birth are adverse perinatal outcomes and important contributors to complex chronic medical conditions ,2. The rGlobally, over 50% of the disability-adjusted life years (DALYs) in 2019 (for the 0–9 year age group) were attributed to LBW and preterm birth . FurtherTo improve perinatal health, the Australian government introduced clinical practice guidelines in 2008 that aimed to provide high-quality evidence-based care for maternity service providers and the consumers of their care . The fivQuality antenatal care (ANC) is one of the core evidence-based interventions in the first 2000 days of the human lifespan . To provWhile ANC is a well-established intervention for pregnancy care, existing research on ANC and perinatal outcomes has primarily focused either on the number of visits or on the timing of the first ANC visit. In addition, how the number of ANC visits impacts differently for women with early versus late entry into ANC has been less researched, and understanding this relationship has important public health policy implications. This study, therefore, aimed to examine the impact of the number of visits and the timing of the first ANC visit on LBW and preterm birth by utilizing regional health data from New South Wales for the period of 2011–2020. The findings from this study may be beneficial for the development and expansion of strategies for evidence-based maternity services to improve birth outcomes.The source of the data utilized in this study was perinatal data that were collected as part of a population-based surveillance system for all births that take place across the state of New South Wales. The data collection has continuously operated since 1990, and the data are collected by attending midwives or medical practitioners. The aim of this data collection is to inform policy and programs for improved maternal and newborn health outcomes. The perinatal data include information on maternal sociodemographics, maternal health conditions, maternal health behaviors, perinatal care, and birth information, including discharge status, birth weight, and gestational age at birth. In SNSWLHD, 14,634 births took place during the period of 2011–2020. A total of 12,941 singleton live births were included in the analysis . For thiThe first outcome variable for this study was low birth weight. Low birth weight was dichotomously coded as ‘1′ if the measured birthweight was <2500 g or ‘0′ if the measured birthweight was ≥2500 g . The secThe first exposure variable for this study was based on the recommended number of ANC visit, as outlined in the Australian pregnancy care guideline . The numThe selection of confounding variables is based on previously published research on LBW and preterm birth ,17,18,19Data analysis was conducted using STATA version 17.0 . The prevalences of LBW and preterm birth, according to the study factors, were estimated. A logistic regression was used to examine the associations between each study factor and the primary outcomes. Multivariable analyses were performed to examine the independent impacts of the recommended number of visits and the timing of the first ANC visit that controlled potential confounders.A staged hierarchical technique  was usedThis study was approved by the Greater Western Human Research Ethics Committee  and the Aboriginal Health and Medical Research Council Ethics Committee . This study was authorized by the Southern New South Wales Local Health District (authorization number: 2022/STE01605).The largest group (27.6%) in the study sample was from the Queanbeyan Health Service . The samOver the study period, 338 (2.6%) LBW and 368 (2.8%) preterm births occurred in SNSWLHD. The prevalences of LBW and preterm birth among young mothers (<20 years of age) were higher . LBW and preterm birth among babies with Apgar scores < 7 were substantially higher than those with scores ≥ 7. The percentage of LBW among mothers who reported diabetes was slightly lower (2.0%). In contrast, preterm birth among diabetic mothers was reported to be higher (3.6%).Multivariable analyses revealed that mothers who received the recommended number of ANC visits were 45% less likely to have LBW ) compared to those who did not receive the recommended number of ANC visits . The eviAs shown in This study identified that the risk of LBW and preterm birth was reduced significantly in babies whose mothers reported an adequate number of visits along with early entry (first trimester) into ANC during 2011–2020. We also found that LBW and preterm birth differed significantly based on medical, social marginalization, and modifiable lifestyle behaviors. The most socioeconomically disadvantaged women had a higher likelihood of LBW and preterm birth. We observed a significant increase in the risk of LBW among Aboriginal mothers and those who reported tobacco smoking. This study revealed that diabetes affects the length of gestational age. Diabetic mothers were more prone to preterm birth compared to their non-diabetic counterparts.The main strength of this study was our sample, which allowed us to examine the effect size of the recommended number of visits compared to the different timings of the first ANC visit while controlling for a range of confounding factors. The sample was selected , along with the recommended number of ANC visits, gave greater protection against LBW and preterm birth. In addition, there was no significant difference in LBW or preterm birth among mothers who attended recommended number of ANC visits but had late entry into ANC (third trimester). Our findings suggest that, to improve perinatal health, efforts should be made to promote both the early entry as well as the recommended number of visits. Such a focus is most likely to benefit women who report smoking during pregnancy, socioeconomically disadvantaged women, and those with Aboriginal backgrounds.


The association between low birth weight and attention problems in childhood has been replicated many times . However birth weight is unlikely the aetiological start-point of this association, as birth weight is itself the product of many prenatal factors e.g. gestational complications, maternal toxin exposure during pregnancy and basic demographics.We explore (1) which prenatal factors best predict attention problems in two independant population-based cohorts of children (2) which associations, if any, are moderated by sex and (3) we report accuracy statistics of our prenatal prediction algorithm for attention problems.Participants were children aged 9 from ABCD study from the United States  and the Growing Up in Ireland (GUI) study from Ireland . Selected variables included familial pscyhiatric history, maternal smoking during gestation, prescription and non-prescription drug-use during gestation and a variety of gestational complications. All interactions with sex were also included. We used 5-fold cross-validation and elastic net regression (glmnet) to identify the optimal predictors of attention problems (measured by CBCL and SDQ).Strongest predictors of attention problems in the U.S. cohort included male sex, number of drugs used during pregnancy, number of family members with a history of mental illness, and number of gestational complications. Sex interacted with several of these risks. Protective factors included being a twin/triplet, being Asian, having higher household income and higher parental education level.Several risk factors for childhood attention problems were identified across both cohorts, supporting their generalizabilty. Other findings were cohort-specific.No significant relationships.