Introduction Although home-visiting programs typically engage families during pregnancy, few studies have examined maternal and child health outcomes during the antenatal and newborn period and fewer have demonstrated intervention impacts. Illinois has developed an innovative model in which programs utilizing evidence-based home-visiting models incorporate community doulas who focus on childbirth education, breastfeeding, pregnancy health, and newborn care. This randomized controlled trial (RCT) examines the impact of doula-home-visiting on birth outcomes, postpartum maternal and infant health, and newborn care practices. Methods 312 young (M = 18.4 years), pregnant women across four communities were randomly assigned to receive doula-home-visiting services or case management. Women were African American (45%), Latina (38%), white (8%), and multiracial/other (9%). They were interviewed during pregnancy and at 3-weeks and 3-months postpartum. Results Intervention-group mothers were more likely to attend childbirth-preparation classes , but there were no differences on Caesarean delivery, birthweight, prematurity, or postpartum depression. Intervention-group mothers were less likely to use epidural/pain medication during labor  and more likely to initiate breastfeeding , although the breastfeeding impact was not sustained over time. Intervention-group mothers were more likely to put infants on their backs to sleep  and utilize car-seats at three weeks . Conclusions for practices The doula-home-visiting intervention was associated with positive infant-care behaviors. Since few evidence-based home-visiting programs have shown health impacts in the postpartum months after birth, incorporating doula services may confer additional health benefits to families. What’s Known on This Subject Research has shown that home-visiting programs have positive impacts in varied domains of parent and child functioning. However, few studies have examined maternal and child health at birth and during the newborn period.What This Study Adds This study, evaluating a home-visiting model that incorporates community doulas into the intervention team, demonstrates improvements in childbirth preparation, breastfeeding initiation, safe sleep practices, and early car-seat use. The intervention was associated with less use of pharmacologic pain control during labor, but not with other indicators of mother and newborn health at birth or improvements in maternal depression.Growing evidence shows that childhood home-visiting programs for socially and economically vulnerable families can have impacts in multiple areas, including maternal and child health, parenting, child development, and family economic self-sufficiency  or case management (control condition). These envelopes had been prepared by the principal investigator before the beginning of the study. Randomization tables were created separately for each community.At 37-weeks of pregnancy, 3-weeks postpartum and 3-months postpartum, mothers were re-interviewed. Families received modest monetary compensation at each session and a baby book and toy at each postpartum session. All study procedures were approved by the Institutional Review Board at The University of Chicago, and the study is registered with clinicaltrials.gov [identifier NCT01947244].After randomization to the intervention group, doula-home-visiting programs assigned families a home visitor  and a community doula. Doulas and home visitors all had deep roots in their communities. All home visitors and doulas had completed at least the foundational training required by their national models, and doulas had completed at least the basic training provided through the Ounce of Prevention Fund. During pregnancy and postpartum, mothers were visited weekly by a home visitor, doula, or both together. The doula worked with the mother more intensively during pregnancy and the first weeks postpartum, while the home visitor became the primary provider by 6 weeks postpartum.Home visitors focused on the mother-infant relationship, child development, child safety, and educational-work planning, as well as screening to make sure that family basic needs were being met. Doulas focused on issues related to pregnancy health, childbirth preparation, breastfeeding, newborn care, postpartum health, and early bonding. Doulas sometimes accompanied mothers to prenatal and postpartum medical visits. Doulas attended births at the hospital where they provided mothers with physical comfort, emotional support, and advocacy during labor and delivery and breastfeeding counseling postpartum. Doulas also offered prenatal classes at the program sites. All programs conducted regular depression screenings and made referrals to mental health consultants.After randomization to the control group, mothers were provided information about case management services in their communities, and case management providers were given mothers’ contact information. In some communities, mothers were referred to existing state-funded case-management providers; in other communities, social-service providers were contracted to provide case management. It was expected that mothers would have at least two meetings with case managers—one during pregnancy and one after birth. Meetings could be in families’ homes, in agency offices, or occasionally by phone. Case managers determined whether families’ basic needs with respect to health, housing, food, employment, education, and childcare were being met, and if needed, made referrals. Case managers screened to identify needs for services regarding substance misuse, depression, and domestic violence.Outcomes were chosen based on Healthy People 2020 maternal and newborn health priorities and outcomes that have been reported in previous studies of doula interventions. Interviews were available in English and Spanish and administered in the mother’s preferred language. Interviewers working in Latinx communities were bilingual. Interviews were usually conducted in families’ homes.At baseline, interviewers asked questions related to the pregnancy, health care, mental health, education and employment, and relationships with family. Baseline interview questions were used to check equivalence of the groups as randomized.At all follow-up interviews, intervention-group mothers were asked about numbers of contacts with doulas and home visitors. All mothers were asked about childbirth preparation class attendance and any other pregnancy/parenting services.At the 3-week postpartum interview (or 3-month interview if mother missed the earlier session), mothers reported on birth outcomes, including pain medication/epidural use during labor, vaginal versus Caesarean delivery, gestational age (GA) at delivery, infant birthweight, NICU admission, length of hospital stay, and mother and/or newborn re-hospitalizations.At the 3-week and 3-month interviews, mothers reported on breastfeeding. Breastfeeding initiation was defined as breastfeeding at least through the hospital stay. Mothers were asked how often they used a car-seat, the positions they used when laying down their infant to sleep and where the infant slept. Mothers reported on depressive symptoms using the Center for Epidemiological Studies-Depression Scale (CES-D) Radloff , dichotot-tests and Chi square tests to check whether randomization was successful. Second, intent-to-treat logistic regression analyses were conducted to examine the impact of the doula-home-visiting intervention on outcomes measured at 37-weeks pregnancy, 3-week postpartum, and 3-months postpartum. Odds ratios, 95% confidence intervals, and one-tailed p-values were calculated for each outcome, using the control group as the reference group. Program site was used as a covariate in all analyses, and any baseline maternal variables that differed between the two groups were used as covariates.First, the intervention and control groups were compared on multiple baseline maternal characteristics measured before randomization using Altogether 436 women were referred to the programs. 312 were enrolled in the sample and randomly assigned to the two conditions. Reasons families were not enrolled included inability to contact, women not wanting to participate in services or the study, women not meeting eligibility criteria, and women at high risk and referred to program services without randomization.Interviews were completed for 256 mothers (82%) at 37-weeks of pregnancy, 283 mothers 91%) at 3-weeks and 278 mothers (89%) at 3-months. Sample attrition was unrelated to program site, race/ethnicity, age, education, co-residence, or prenatal depressive symptoms. There were no differences in sample attrition at either follow-up interview between the intervention and control groups. Figure % at 3-wep < .05). Co-residence with parent figure was a control variable in all analyses.Participants in the baseline interview were young and low-income, with almost half identifying as black/African American 45%, n = 140) and just over a third Latina/Hispanic . 11% of mothers preferred to be interviewed in Spanish. Most mothers were in their second trimester of pregnancy and expecting their first child. Over two-thirds were partnered  with the father of the baby . Table 40 and juVirtually all mothers  assigned to the doula-home-visiting group received at least one home visit. Among mothers interviewed at 37 weeks, the average number of doula visits prior to 37 weeks was 8.9 (SD = 6.9) and the average number of visits from a home visitor was 5.8 (SD = 4.8). Doulas were present in the hospital for 75% (n = 106) of the births. By 3-months postpartum, 131 (92%) mothers had received at least one postpartum visit from their doula and 120 (84%) had received at least one postpartum visit from their home visitor.Results from logistic regression analyses using one-tailed hypothesis tests Table  show thaThe intervention was not associated with preterm births (GA < 37 weeks), low birthweight, NICU admission, length of newborn hospital stay, re-hospitalization of infants, having a pediatrician or pediatric clinic at 3 weeks, or having a well-baby check up by 3 months. Almost all families in both groups reported having a pediatrician for their infants (98%), and all mothers reported taking their infant in for at least one well-baby check up by 3 months of age.p = .07). There were no group differences on breastfeeding, sleeping or car seat use at 3 months.Mothers in the intervention group were more likely to initiate breastfeeding in the hospital . At 3 weeks, mothers in the intervention group were more likely to always place their infants on their backs for sleeping  and to always put their infants in a car seat when traveling by car . There was a non-statistically-significant trend for infants in the intervention group to have their own beds (OR 1.44, 95% CI 0.89–2.34, Although most early-childhood home-visiting programs begin working with families during pregnancy or soon after birth, relatively few evaluations have examined maternal and child health outcomes at birth or during the newborn period. The doula-home-visiting model, in which a community doula partners with a home visitor during pregnancy and through 6-weeks postpartum, provides greater emphasis on pregnancy health, childbirth, breastfeeding, and newborn health than most other home-visiting models, and additionally, offers hospital-based support during childbirth and agency-based childbirth preparation classes. This RCT shows that the doula-home-visiting intervention has impacts on childbirth preparation, epidural/pain medication use during labor, breastfeeding, and safe newborn-care practices.Mothers receiving the intervention were more likely to have attended a childbirth preparation class. Although virtually all mothers in the sample had opportunities to attend childbirth classes through prenatal clinics and hospitals, few control-group women took advantage of such opportunities. Half of the women in the intervention group participated in such classes either at clinics and hospitals or through weekly classes offered by their home-visiting programs. Moreover, all mothers who were visited by a doula also received individualized childbirth education at home. Perhaps as a result of this preparation and the presence of the doula during labor, mothers in the intervention group were less likely to use pharmacologic pain relief during labor, a finding similar to other studies of doula labor support (Hodnett et al. Mothers in the intervention were more likely to initiate breastfeeding, consistent with previous research on community doulas (Edwards et al. The doula-home-visiting intervention did not show impacts on postpartum maternal depressive symptoms, consistent with findings from most other home-visiting evaluations. Postpartum depression is powerfully influenced by a complex set of biological factors, chronic stress, trauma history, and instability in relationships with infants’ fathers and have been challenging to prevent (Edwards et al. Mothers in the intervention were more likely to always place their newborns on their backs to sleep and always use a car-seat. Few previous home-visiting studies have looked at early infant safety practices. Although the present study does not address the manner in which mothers received these safety messages, previous research suggests that low-income mothers may reject infant sleep recommendations, for example, because of distrust of health professionals, reliance on advice from family members, and concern for infant comfort (Colson et al. Notably, although doula-home-visiting impacts on newborn care practices were found in the first weeks postpartum, group differences diminished by 3 months. It may be that over time families chose infant feeding or sleeping practices they felt were most effective for their family circumstances or infant preferences. It may be that as home visitors took over intervention work from the doulas, the focus of the work shifted from feeding and sleep practices to other important areas such as responsive parenting, child development, and mother’s personal development.Finally, although the present study has many methodological strengths—a randomized design implemented within programs taken to scale in real agency settings, it also has limitations. The sample drew from only four programs in a single state and excluded adolescents at the most extreme levels of risk. Because data in this paper were provided through mother report and not administrative records, reliable information on important medical procedures and outcomes during labor, such as qualifications of health providers and Apgar scores, were unavailable. Because each mother in the intervention group was offered services from a doula and home visitor team, the independent contribution of the two different providers could not be determined. The sample was underpowered to detect important, but relatively rare maternal and child health problems, particularly infant mortality. Nevertheless, the study identified impacts on important maternal and newborn health outcomes that have rarely or never been found in other evaluations of home-visiting models. Future research should focus on a broader set of health outcomes, including outcomes documented through administrative records, and examine the processes through which doulas convey health information, contrasting their role to home visitors who are not doulas.Consistent with an already strong evidence base regarding birth doula interventions and a smaller body of work on community doulas, the present study shows improved maternal and child health when mothers have access to doula services through community-based home-visiting programs. However, there are presently funding barriers to increasing low-income women’s access to doula services. Simple steps to improving access would be for states to recognize community doula services as evidence-based interventions eligible for existing home-visiting funding, as has been the case in Illinois, and also to develop state certification processes and other mechanisms for using Medicaid funds to reimburse for doula services, as has happened in Oregon and Minnesota Gay .


Specialised preterm birth clinics care for women at high risk of spontaneous preterm birth. This systematic review assesses current practice within preterm birth clinics globally.A comprehensive search strategy was used to identify all studies on preterm birth clinics on the MEDLINE, Embase, PsycINFO, CENTRAL and CINAHL databases. There were no restrictions to study design. Studies were limited to the English language and publications from 1998 onwards. Two reviewers assessed studies for inclusion, performed data extraction and reviewed methodological quality. Primary outcomes were referral criteria, investigations and interventions offered in preterm birth clinics. Secondary outcomes were the timing of planned first and last appointments and frequency of review.Thirty-two records fulfilled eligibility criteria and 20 studies were included in the main analysis following grouping of records describing the same study or clinic. Studies were of mixed study design and methodological quality. A total of 39 clinics were described; outcome data was not available for all clinics. Referral criteria included previous spontaneous preterm birth , previous mid-trimester loss  and previous cervical surgery . All clinics offered transvaginal cervical length scans. Additional investigations varied, including urogenital swabs  and fetal fibronectin . The primary treatment of choice for a sonographic short cervix was cervical cerclage in 10/33 (30%) clinics and vaginal progesterone in 6/33 (18%), with 10/33 (30%) using multiple first-line options and 6/33 (18%) using a combination of treatments. The majority of clinics planned timing of first review for 12–16 weeks  and the frequency of review was usually determined by clinical findings . There was a wide variation in gestational age at clinic discharge between 24 and 37 weeks.There is variation in the referral criteria, investigations and interventions offered in preterm birth clinics and in the timing and frequency of review. Consistency in practice may improve with the introduction of consensus guidelines and national preterm birth prevention programmes.Systematic review registration number: CRD42019131470. Preterm birth is the leading cause of neonatal death and is associated with significant perinatal morbidity and lifelong health consequences . PretermPreterm birth clinics provide focused and specialised obstetric care to asymptomatic women at increased risk of preterm birth due to their obstetric or gynaecological history. The key components include addressing modifiable risk factors , surveillance of cervical length by transvaginal ultrasound scan through the mid-trimester, and providing evidence-based interventions when indicated. The use of transvaginal cervical length assessment and quantitative fetal fibronectin have been proven to aid prediction of spontaneous preterm birth in asymptomatic high risk women and can be used to guide management decisions , 7. InteAlthough there is good evidence to support many of the practices that occur in preterm birth clinics, specific evidence to support the utility of preterm birth clinics as a whole is still evolving . Two preUntil recently there were no national or international guidelines on the protocols and care pathways to be used in preterm birth clinics, and practice is often based on local expert opinion. The newly released (2019) ‘Reducing Preterm Birth: Guidelines for Commissioners and Providers’ from the UK Preterm Clinical Network provides guidance on referral pathways for preterm birth prevention . This inThis systematic review aims to assess the referral criteria and investigations and interventions offered in preterm birth clinics internationally and the planned timing and frequency of review. It does not attempt to prove the efficacy of preterm clinics as it has already been established that there is currently inadequate evidence available , 12. TheTo assess the eligibility criteria used for referral to preterm birth clinics.To assess the types of investigations offered in preterm birth clinics.To assess the types of interventions offered in preterm birth clinics.To assess the planned frequency and timing of review in preterm birth clinics.This systematic review has four objectives:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=131470. This systematic review has been conducted in line with the standard Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and written according to the PRISMA checklist of items to include when reporting a systematic review [The protocol was prospectively registered with the PROSPERO International Prospective Register of Systematic Reviews in May 2019, registration number CRD24019131470, available at c review .All studies on preterm birth clinics were eligible for inclusion, including those that assessed a clinic indirectly i.e. by assessing another intervention in a high risk population cared for in a preterm birth clinic. Preterm birth clinics are also known as preterm birth prevention clinics, preterm surveillance clinics, specialised preterm birth clinics, dedicated preterm birth clinics, miscarriage follow-up clinics and specialised antenatal clinics. There is no comparator group in this review due to the nature of the research objectives. Studies on other types of specialised antenatal clinics such as for multiple pregnancy, hypertension and diabetes were excluded.There were no restrictions placed on the types of studies eligible for inclusion and both quantitative and qualitative research methods were included. Examples of study designs include randomised controlled trials, cohort studies, case-controlled studies, cross-sectional studies, interviews, surveys and focus groups. Studies were restricted to those published in the English language, for feasibility, and to publications from 1998 onwards, as this is when the first modern-day preterm birth clinic was established.Eligibility criteria for referral .Types of investigations offered, defined as any test arranged or carried out from the clinic with the aim of reducing the risk of spontaneous preterm birth or improving perinatal outcomes from preterm birth . Investigations that form part of standard antenatal care that are not aimed at reducing the risk of spontaneous preterm birth were excluded .Types of interventions offered, defined as any surgical, medical or non-medical therapy used with the aim of reducing the risk of spontaneous preterm birth  or with the aim of improving perinatal outcomes for babies that are born preterm .The primary outcome measures are:4.Timing of planned first and last clinic visit (measured in weeks and days of gestation).5.Frequency of planned clinic review (measured in number of days or weeks).The secondary outcomes measures are:The MEDLINE, Embase, PsycINFO, CENTRAL and CINAHL databases were searched on 1 May 2019. Additional studies were identified by hand-searching reference lists of included publications.A comprehensive search strategy was developed using the Peer Review of Electronic Search Strategies (PRESS) Guidelines  and was References identified from each database search were imported into EndNote X8 referencing software  and thenElectronic data collection forms were used to extract and record data from included studies. Data collection was performed by one reviewer and cross-checked by a second reviewer. Authors were contacted for the names and locations of included preterm birth clinics when this was not reported.Primary and secondary outcomes previously specified were collected. Other data items include study source information and funding details, study design, study timeframes, demographic details, risk factors for spontaneous preterm birth, and spontaneous preterm birth rates.Two reviewers assessed the methodological quality of included studies. The Cochrane Risk of Bias Tool  was usedPrimary and secondary outcomes are described as proportions.The majority of studies included UK based preterm birth clinics, and some reported on multiple clinics. To ensure we avoided over-representation of clinics described in more than one study, authors of UK studies that reported on unnamed clinics were approached –26. ThisThe study selection process is detailed in Fig. Of the 20 included studies, 15 were full text articles , 49–56 aResults of the methodological quality assessments are shown in Additional file The study characteristics and primary and secondary outcomes are summarised in Table 23 and six clinics from individual clinic studies outside of the UK [Data from 39 clinics were combined to assess the primary and secondary outcomes; 33 UK based clinics from Care 2019f the UK , 49–53. Preterm birth clinic referral criteria is described in Table Group B streptococcus, serum thyroid stimulating hormone and alkaline phosphatase which were each described in one clinic.Data on the types of investigations offered were available for 28 clinics . All clinics performed transvaginal cervical length ultrasound scans, however use of additional investigations was variable. Urogenital swabs were the second most common investigation performed, with 16/28 (57%) clinics routinely offering this. Fetal fibronectin was used as a risk assessment tool in asymptomatic women in some clinics . Other investigations included urine culture, rectal culture for There were differences in how interventions aimed at reducing the risk of spontaneous preterm birth were reported. Table Various measures were used to define the threshold for treatment of a ‘short’ cervix. The most common threshold was a cervical length of < 25 mm . A cervical length of < 15 mm or use of centile charts were used less frequently . A further 4/38 clinics (11%) used a combination of thresholds with centile charts and/or a cervical length of < 25 mm. Results from the QUiPP App, which combines clinical history, cervical length measurements and fetal fibronectin  were useThe use of additional interventions such as hospital admission, antenatal corticosteroid therapy and antimicrobials for high risk, asymptomatic women was not consistently reported across studies and these data were not available from the large surveys of practice in the UK; thus accurate synthesis of information was not possible. Data on additional interventions are provided in Tables Many clinics also provided routine lifestyle recommendations. Of the 22 clinics , where these data were available, almost half  routinely advised restriction of physical activity, 6/22 (27%) recommended stopping work, 9/22 (41%) advised refraining from sexual intercourse and 6/22 (27%) made dietary recommendations. No clinic recommended routine bed rest and 8/22 (36%) clinics reported that no additional advice was given.Table Data was obtained for a number of preterm birth clinics in this systematic review. The majority of clinics were located in the UK, but clinics in America, Germany, Italy and Australia are also identified. All clinics accepted referrals for women with a previous spontaneous preterm birth, however other referral criteria varied. The majority of clinics saw women with previous mid-trimester loss, previous preterm pre-labour rupture of membranes, previous cervical surgery, uterine abnormality or malformation, and a short cervix detected in pregnancy. A minority of clinics also accepted referrals for other indications including history of multiple surgical terminations of pregnancy or dilatation and curettage, as follow up after a diagnosis of threatened preterm labour, and presence of an autoimmune condition. Of interest, no clinic listed previous caesarean section at full dilatation as a referral criteria, despite recent evidence that this is a significant risk factor for spontaneous preterm birth , 57.Transvaginal cervical length scans were used to aid decisions on management in all clinics but the use of additional investigations such as urogenital swabs, urine culture and fetal fibronectin varied. Differences in how interventions were reported limited the ability to synthesise these results, however available evidence shows that a range of interventions are available, with significant variation in the choice of primary management for a sonographic short cervix within the UK, where this data was available. The majority of clinics saw women for their first appointment between 12 and 16 weeks of gestation and cared for them through to the late second or early third trimester. The frequency of preterm birth clinic review was usually directed by clinical findings.To the best of our knowledge, this is the first systematic review to assess practice in preterm birth clinics globally, and has shown wide variation in most aspects of care. Inconsistencies in care have also been identified as an issue in national surveys of practice in the UK , 40. ThiImproving consistency in care will also allow clinics to combine their outcome data in a more meaningful way, enabling high-quality research into the effectiveness of interventions provided in preterm birth clinics, along with comparisons between clinics . The UK The main limitation of this review is the potential for incomplete data. Due to the paucity of literature in this area, studies were included that did not specifically assess or report on care in a preterm birth clinic, but reported on another aspect of care in a group of high risk women cared for in a preterm birth clinic. Thus, details about the clinic itself were at times incomplete. We have assumed for the purposes of this review that if a referral criteria, investigation or intervention was not reported, then it was not used. Another limitation is that included data is predominantly from clinics in the UK, so results are likely to favour practice from this region. This is unsurprising as the UK have led the development of modern-day preterm birth clinics and to our knowledge, are the first to recommend the use of preterm birth clinics in national guidelines . ResultsWe have taken a unique approach to analysis by combining different studies on the same clinic and in our selection of studies suitable for combination and synthesis. This was necessary as the ‘population’ of interest was the clinic itself, and thus inclusion of all studies would have resulted in over-representation of certain clinics which were described in multiple studies. The assumption that the three clinics reported in other included UK based studies were included within the four anonymous clinics in Care 2019, is a further limitation of this study. However even if not the case, this is unlikely to have changed findings significantly.To our knowledge, this is the first systematic review of the practice of preterm birth clinics internationally. Variation in the referral criteria, investigations and interventions, and timing and frequency of review in individual preterm birth clinics was evident. Consistency in care is likely to be improved with the introduction of consensus guidelines and national preterm birth prevention programmes such as those recently introduced in the UK. A repeat survey of practice in preterm birth clinics in the UK can be used to assess the impact of new consensus guidelines introduced in the UK, and are also required in other localities.Additional file 1: Table S1. MEDLINE search strategy. Table S2. Methodological quality assessment of included studies based on the Newcastle-Ottawa Scale for cohort and case controlled studies. Table S3. Methodological quality assessment of included studies based on the modified Newcastle-Ottawa Scale for cross-sectional studies. Table S4. Methodological quality assessment of included studies based on the Cochrane Risk of Bias Tool for randomized controlled trials. Table S5. Methodological quality assessment of included qualitative studies based on the Critical Appraisal Skills Programme Checklist for qualitative research.


The clinical management of breech presentations at term is still a controversially discussed issue among clinicians. Clear predictive criteria for planned vaginal breech deliveries are desperately needed to prevent adverse fetal and maternal outcomes and to reduce elective cesarean section rates. The green-top guideline considers an estimated birth weight of 3.8 kg or more an indication to plan a cesarean section despite the lack of respective evidence.To compare maternal and neonatal outcome of vaginal intended breech deliveries of births with children with a birth weight of 2.5 kg– 3.79 kg and children with a birth weight of 3.8 kg and more.Prospective cohort study.All vaginal intended deliveries out of a breech position of newborns weighing between 2.5 kg and 4.5 kg at the Obstetrics department at Goethe University Hospital Frankfurt from January 2004 until December 2016Neonatal and maternal outcome of a light weight group (LWG) (< 3.8 kg) was compared to and a high weight group (HWG) (≥ 3.8 kg) using Pearson’s Chi Square test and Fishers exact test. A logistic regression analysis was performed to detect an association between cesarean section rates, fetal outcome and the birth weight.No difference in neonatal morbidity was detected between the HWG  and the LWG . Cesarean section rate was significantly higher in the HWG with 45.2% in comparison to 28.8% in the LWG with an odds ratio of 1.57 . In vaginal deliveries, a high birth weight was not associated with an increased risk of maternal birth injuries )A fetal weight above 3.79 kg does not predict increased maternal or infant morbidity after delivery from breech presentation at term. Neither the literature nor our analyses document evidence for threshold of estimated birth weight that is associated with maternal and/or infant morbidity. However, patients should be informed about an increased likelihood of cesarean sections during labor when attempting vaginal birth from breech position at term in order to reach an informed shared decision concerning the birth strategy. Further investigations in multi center settings are needed to advance international guidelines on vaginal breech deliveries in the context of estimated birth weight and its impact on perinatal outcome. The management of breech presentations at term is a controversially discussed topic in obstetrics. Several large cohort studies reported a lower neonatal morbidity and mortality when infants were delivered by planned cesarean section –4. In coPlanned cesarean sections are increasing worldwide. Associated short—and long-term complications like hemorrhage, uterine rupture, and abnormal placentation parallel these rising procedure numbers –9. ThereThe presented prospective cohort study includes 1054 participants who intended vaginal breech delivery at term and analyzes maternal and fetal outcomes when singletons with a birth weight of 2.5 kg to 3.79 kg (n = 888) were delivered compared to children weighing 3.8 kg (n = 166) and more. Because of an exclusion from the vaginal birth approach in most clinical management regiments we hypothesize an increased maternal and neonatal morbidity for children born out of a breech position weighing 3.8 kg– 4.49 kg.A prospective cohort study was performed on the cohort of women presenting with breech at term (>37 weeks) at the Goethe University Hospital Frankfurt, Germany from January 2004 to December of 2016. The ethics committee of the Goethe University Hospital Frankfurt approved of the study protocol (Reference number 420/11). The requirement for patients informed consent was waived by the committee as all data was obtained within the hospitals standard care of patients intending a vaginal breech delivery. Patients received treatment as usual and only clinically relevant and required data was documented. Data was extracted from treatment files and anonymized by treating obstetricians who are part of the ethics committee approved study team. The ‘Perinatalerhebung Hessen’, a state database was used to obtain the data. Missing data, the mothers’ patient history as well as diagnoses and outcome parameters of neonates who were admitted to the neonatal intensive care unit (NICU) were gathered using the hospitals patient management system. All data was acquired and set into a table for analysis within this study after the patients were discharged. Of 1743 cases with a breech presentation at term 1054 expecting women intended a vaginal birth approach and did not meet exclusion criteria. Exclusion criteria were planned cesarean delivery , insulin-treated diabetes, infant’s birth weight of over 4.49 kg or less than 2.5 kg. Women with breech presentation register for birth and delivery planning at the outpatient clinic at 34 to 36 weeks of gestation Vaginal delivery approach from breech position was offered in case of a successful previous vaginal birth or an obstetrical conjugate above 12 cm (measured by MRI) and an estimated birth weight of 2.5 kg or more of a proportional grown fetus. Weight of the fetus of ≥3.8kg, previous cesarean delivery or head flexion did not lead to exclusion.Louwen et al. showed a superior maternal and fetal outcome from birth position on knees and arms or in upright position  The pref1054 women intended vaginal delivery from breech position and their babies weighed 2.5 kg to 4.49 kg at birth. There were no outliers. The Shapiro-Wilk-W-Test documents normal distribution of birth weights. (W = 0.987) 723 cases resulted in vaginal delivery. Within this group of successful vaginal births, the fetal weight was normal distributed (Shapiro-Wilk-W-Test W = 0.986) and there were no outliers.Differences in birth weight-dependent variables e.g. duration of pregnancy is displayed only descriptively. Epidemiological data–for instance BMI and the mother’s age–was tested using student’s t-test with welch correction in cases of unequal variances.2 test and Fishers exact test.Group differences in rates determining the fetal or maternal outcome as well as the calculated scores (modified PREMODA score) were tested in univariate contingency table based statistics using Pearson’s χThe birth weight’s influence on outcome variables as well as the probability to receive a cesarean section was tested using a univariate logistic regression analysis.Multivariate analyses were performed using a nonparametric Spearman’s ρ testing and are shown in a supplementary table All statistical analyzes were carried out using JMP software .We report of 1054 deliveries out of breech position. Mean fetal birth weight was 3351g.  To groups were generated according to fetal weight. 1) The low fetal weight group  and 2) the high fetal weight group . Maternal mean age  and body mass index (BMI) of both groups were not significantly different, however the high birth weight group descriptively showed higher BMI values.  Duration of pregnancy was significantly longer in the HWG (40.4 weeks respectively 39.4 weeks in the LWG). Parity was equally distributed in both groups as well as subtypes of breech positions. In both groups, the frank breech was the most common position. Cesarean section rate was significantly higher in the HWG with 45.2% in comparison to 28.8% in the LWG with an odds ratio of 2.0  see. Comparing the outcome of newborns between the LWG and the HWG did not reveal a disadvantage for neonates weighing 3.8 kg or more. There was no difference between groups regarding the frequency of 5 minutes APGAR below 4 , the stay on a neonatal intensive care unit (NICU) over 4 days  or birth trauma . Moreover there were no differences in numbers of neurologic deficits  or perinatal asphyxia . .For a clear analysis a score adapted from the PREMODA study  was applA multivariate analysis of this cohort including fetal birth weight, delivery mode, pregnancy duration, parity and maternal BMI could not detect a correlation of those factors with fetal morbidity. The strongest correlation was found between fetal birth weight and pregnancy duration (ρ = 0.461 p>0.0001). However this analysis shows a positive correlation of the maternal BMI and the cesarean section rate (ρ = 0.115 p = 0.0002)  All cases of neonates with a birth weight of 2.5 kg– 3.79 kg  were compared to all cases of newborn weighting 3.8 kg– 4.49 kg .Birth position in both groups were equally distributed. In 16.4%, patients delivered in dorsal position in the vLWG compared to 22% in the vHWG. In 43.2% a maneuver to assist the body and/or the head was necessary in the vLWG compared to 45.0% in the vHWG (no significant difference). The odds ratio for a manually assisted vaginal delivery was of 1.08 (95% CI 0.7–1.7) for neonates weighing 3.8 kg or more. .Neonatal outcome analyses were performed using the same independent variables as mentioned above. Rates of birth trauma, long stays on the NICU (> 4 days), short time problems with adaption, intubation or perinatal asphyxia were not significantly different between vaginal birth groups. Calculating the severe morbidity and mortality rate using the modified PROMODA score  for both groups revealed no disadvantage for the vHWG (3.3%) in comparison to the vLWG (2.5%)  .A birth weight of 3.8 kg or more was not associated with a higher rate of perineal tears ); When grades of perineal tears were compared between weight groups though, the perineal tear grade III and IV rate was descriptively but not statistically significantly higher in the vHWG ). There were no significant differences between groups regarding rates of vaginal or labial injuries, episiotomies or application of peridural anesthesia during labor. A multivariate analysis including the following covariates within the group of successful vaginal deliveries was performed: Fetal birth weight, perineal injuries, fetal morbidity, maternal BMI, pregnancy duration, parity and the need to perform assisting maneuvers. Here we found a weak positive correlation of fetal morbidity and the need to perform assisting maneuvers  and a weak correlation of perineal tears and fetal birth weight  ).  AccordinAll statistical analyzes were additionally performed with equal sample sizes. We compared the HWG / vHWG to a subgroup of automatized randomly chosen 166 (HWG) / 91 (vHWG) cases out of the respective control group. Here, no other results have been obtained with regards to content if not indicated otherwise within the respective Fig (Data not shown)et al [Obstetric management of breech presentation at term is not uniform and up to now it is a controversially discussed issue whether a cesarean or a vaginal delivery is to be recommended. The reasons are missing evidence based guidelines and contradicting publications about this matter. E.g. the Term Breech Trial by Hannah et al  found vaet al –18. Meanet al . In ordeEvaluating all deliveries and their fetal outcomes using a modified PREMODA score, a higher morbidity for children weighing over 3.79 kg could not be shown. Neither analyzes of all vaginal indented deliveries out of a breech position at term  nor analTo quantify adverse outcomes of neonates, a modified PREMODA score was used. All single cases covered by this score were looked upon in detail. This excluded cases with adverse outcomes where the mode of delivery was not relevant to the neonate’s condition. Some hereditary conditions are associated with macrosomia or growth restriction, posing as a possible bias–these cases were excluded in order to purify our analysis of perinatal morbidity.We saw a non-significant tendency for heavier children to produce more higher-graded perineal tears. A higher birth weight is known to be associated with a higher rate of perineal tears in cephalic deliveries.  Here, inThe likelihood to result in cesarean section correlates positively with the birth weight in vaginal planned deliveries. , Fig 2 WThe role of the maternal BMI, pregnancy duration and parity in obstetrics and perinatal morbidity is well known –26. WhenA recommendation to plan cesarean section in advance is not indicated in breech presentations at term with an estimated fetal birth weight of over 3.79 kg since perinatal morbidity does not differ. Nevertheless likelihood to receive a cesarean should be discussed with expecting women. The breech position of the baby is as itself a reason for an elevated cesarean section rate compared to cephalic deliveries which is due to limited options to accelerate birth in cases of birth delay or abnormal fetal cardiography. In cephalic deliveries, e.g. a micro-blood analysis can be performed to exclude fetal acidosis or an operational vaginal delivery can be performed to accelerate birth. As in breech deliveries comparable methods are not established leading to increased cesarean section rates, expecting women have to be informed. The cesarean section rate probabilities and their changes due to a) the fetal position and b) the birth weight should be addressed in birth mode planning medical appointments.It has been shown that cesarean section after onset of labor is favorable compared to planned cesarean section in regard of long term fetal outcome.  ThereforA weakness of our study method might be that the estimated birth weight and the actual birthweight can differ up to 15%  and is eAnother limitation of this study is that the acquired data is based on a single center. Since quality standards in obstetric departments and regional cesarean section rates are differing quite largely, some of our findings (mostly concerning cesarean section rates) may not be applicable or reproducible in any other hospital or country. The outcome of vaginal deliveries out of a breech position depends on the obstetrician’s expertise. In order to implement vaginally intended breech deliveries into clinical practice it needs more education and a growing number of hospitals offering a vaginal birth approach.This study gives detailed analyses of a large collective of breech deliveries at term in our center in Frankfurt from 2004 until 2016. However the data is based on one center only impact on guideline development and clinical practice may be limited. Randomized controlled trials with large patient cohorts in multi-center settings are needed in order to supply data for evidence based guidelines.S1 File2), parity, mod. PREMODA Score, fetal birth weight (g). Figure B) Multivariate analysis of all successful vaginal deliveries (n = 723) including the following variables: perineal injury (yes or no), fetal birth weight (g), mod. PREMODA Score, assisted delivery , maternal BMI (kg/m2), pregnancy duration (days), parity. Spearman’s ρ coefficient and p values are indicated.Weak correlation indicated by brown coefficient (from 0.1 to 0.29) Moderate correlation indicated by red coefficient (from 0.3 to 0.49) 30 BMI values are missing. Figure A) Multivariate analysis of all vaginally intended deliveries (n = 1053) including the following variables: Pregnancy duration (days), maternal BMI (kg/m(DOCX)Click here for additional data file.


Fetal growth restriction is, despite advances in neonatal care and uptake of antenatal ultrasound scanning, still a major cause of perinatal morbidity. Neonates with birth weight > 10th percentile are assumed to be appropriate-for-gestational-age (AGA), although many are at increased risk of perinatal morbidity, because of undetected mild restriction of growth potential. We hypothesized that within AGA neonates, reduced fetal growth velocities are associated with adverse neonatal outcome.A retrospective cohort study of singleton pregnancies, in the Maastricht University Medical Centre (MUMC) between 2010 and 2016. Women had two fetal biometry scans  and delivered a newborn with a birth weight between the 10th–80th percentile.Differences in growth velocities of the abdominal circumference (AC), biparietal diameter (BPD), head circumference (HC) and femur length (FL) were compared between the suboptimal AGA (sAGA) (birth weight centiles 10–50) and optimal AGA (oAGA) (birth weight centiles 50–80) group. We assessed the association between velocities and neonatal outcomes.p < .001), HC 10.50 ± 0.80 vs 10.68 ± 0.77 (p = 0.001), BPD 3.01 ± 0.28 vs 3.08 ± 0.27 (p < .0001) and FL 2.47 ± 0.21 vs 2.50 ± 0.22 (p = 0.014), compared to the optimal AGA group. Neonates with an adverse neonatal outcome had significantly lower growth velocities (in mm/week) of: AC 10.57 vs 10.94 (p = 0.034), HC 10.28 vs 10.59 (p = 0.003) and BPD 2.97 vs 3.04 (p = 0.043) compared to those with normal outcome. An inverse association was observed between the AC velocity and a composite adverse neonatal outcome (OR) = 0.667 , and between the AC velocity and neonates with NICU stay (OR) = 0.733 . Neonates with a birthweight lower than expected  had significantly more composite adverse neonatal outcomes 8.5% vs 5.0% (p = 0.047), NICU stays 9.6% vs 3.8% (p < .0001) and hospital stays 44.4% vs 35.6% (p = 0.006).We included 934 singleton pregnancies. In the suboptimal AGA group, fetal growth velocities were lower (in mm/week): AC 10.72 ± 1.00 vs 11.23 ± 1.00 (Appropriate-for-gestational-age neonates are a heterogeneous group with some showing suboptimal fetal growth. Abnormal fetal growth velocities, especially abdominal circumference velocity, are associated with adverse neonatal outcome and can potentially improve the detection of mild growth restriction when used in multivariate models. There is a subgroup within appropriate-for-gestational age neonates, who are at increased risk of perinatal morbidity. The abdominal circumference velocity could be a detector for this group with mild growth restriction.Fetal growth restriction (FGR) is one of the most frequently encountered problems in modern obstetrics, with a major impact on perinatal mortality and morbidity . FGR is Literature has often interchangeably used the terms ‘intrauterine growth retardation’, ‘intrauterine growth restriction’ (both given the acronym IUGR) and fetal growth restriction (FGR), to indicate abnormally small fetus suspected antenatally, based on ultrasound parameters of fetal growth, most commonly expected fetal weight (EFW) and abdominal circumference (AC) . We prefThese definitions are based on cut off points and statistical assumptions derived from epidemiological data, rather than being derived from physiopathological mechanisms. It is conceivable that the mechanism restricting fetal growth can have variable severity, leading in mild cases to a decrease in growth velocity but not enough for birth weight to drop below the 10th centile. Hence, these neonates with restricted growth potential are falsely labelled as appropriate-for-gestational age (AGA) according to many commonly used population charts.Unlike severe early FGR, mild and late onset FGR in the AGA group is difficult to diagnose and more elusive to currently used predictive tests , 5. FetuIn this retrospective cohort study, we combined data from two electronic patient databases: the antenatal ultrasound database and the labour ward database of the Maastricht University Medical Centre (MUMC) to make an integrated database. We included women with singleton pregnancies without congenital anomalies, who delivered between April 2010 and July 2016 in the Maastricht University Medical Centre, and who had two available fetal growth scans, one between 18 and 22 weeks of gestational age and one between 30 and 34 weeks of gestational age. The pregnancies were dated according to the formula of Robinson calculated from crown-rump length (CRL) measurement in the first trimester . We onlyAt the first hospital intake, data on length, weight, smoking status and medical and obstetric history, were collected and recorded in an electronic medical file. Body mass index was calculated by weight (kg) divided by height (m)-squared. An experienced sonographer recorded ultrasound measurements of abdominal circumference (AC), biparietal diameter (BPD), head circumference (HC) and femur length (FL), using a GE Voluson ultrasound machine, with a 2-5 MHz curved-array transducer, in accordance with the routine mid-trimester fetal ultrasound scan guidelines . These fIn addition, we compared neonatal outcomes in two groups of neonates based on the premise that a fetus with an above average abdominal circumference at 20 weeks of gestation is “expected” to have an above average birth weight, and vice versa. Consequently, the first group consisted of neonates who had a below average birth weight despite an above average AC at 20 weeks (birth weight < expected), suggesting a late reduction in growth velocity, and the second group consisted of neonates who had a higher than average birth weight despite a below average AC at 20 weeks (birth weight ≥ expected).Delivery and neonatal outcomes were registered by the obstetrician or in case of an adverse outcome by the paediatrician. Data about induction of labour and mode of delivery were collected. Mode of delivery was divided in subcategories; spontaneous vaginal, assisted vaginal, intrapartum- or prelabour caesarean. All deliveries were in the same hospital.APGAR-scores were assessed at 1 and 5 min after birth. We used a cut-off of less than 5 at 5 min to determine adverse outcome . MetabolThe general characteristics were presented as mean and standard deviation (SD) for the total cohort and stratified by birth weight percentiles  group, and the birth weight percentiles 10–50 as suboptimal appropriate-for-gestational-age (sAGA) group).P-values of 0.05 or less were considered to indicate statistical significance.Differences between the groups were calculated with the independent T-test for continuous variables and the Chi-square test for categorical variables. Analysis of variance (ANOVA) was used to compare growth velocities between different groups of birth weight percentiles. Post-hoc testing of differences was corrected for multiple testing using the Bonferroni-method. Growth velocities we reported using mean, SD and range. We used logistic regression analysis to estimate the association between abdominal circumference velocity and dichotomous neonatal outcomes, corrected for potential confounders. We considered maternal age, BMI and parity as potential confounding variables. All analyses were performed using SPSS Statistics 23 . n = 2.762), between 22 and 30 weeks of gestational age (n = 5.641) and > 34 weeks of gestational age (n = 3.789). After exclusion of twin pregnancies (n = 362), we had 7.348 singleton pregnancies in the labour ward database and 16.457 fetal biometry scans between 18 and 22 and 30–34 weeks of gestational age in the antenatal ultrasound database.Between April 2010 and July 2016, we identified 7.720 pregnant women, with 28.649 fetal biometry scans. We excluded scans < 18 weeks of gestational age (n = 953) or birth weight percentile > 80 (n = 213), as well as those with intra-uterine fetal death (n = 18) and congenital anomalies  (n = 116).After cross-matching the two databases, women with growth scans outside the range of the intended periods or who delivered outside the MUMC hospital were excluded. Also, we excluded neonates with a birth weight percentile < 10 (n = 569) and birth weight percentile 50–80, considered as optimal appropriate-for-gestational-age (oAGA) (n = 365).The final study cohort consisted of 934 singleton pregnancies (birth weight centiles 10–80) and 1.868 fetal ultrasound biometry scans , except a lower percentage of ovulation induction (2.5% vs 0.7%) (p = 0.025). There was an obvious difference in birth weight (g) between the groups: 3425.4 ± 421.6 (1440–4125) in the optimal AGA vs. 3041.5 ± 402.3 (1353–3818) in the suboptimal AGA group (p < 0.001).The baseline characteristics of the study population are given in Table p < .001), head circumference , biparietal diameter  and femur length , respectively. Within the sAGA neonates, the difference in growth velocity (in mm/week) was most prominent among the subgroup with the lowest birth weight percentiles (i.e. BW p10–16) for AC , HC  and BPD  compared to the oAGA reference group .Compared to oAGA neonates (BW p50–80), the sAGA group (BW p10–50) had reduced growth velocities across all studied parameters (in mm/week) Table : abdominp = 0.034), head circumference 10.28 ± 0.99 vs 10.59 ± 0.79 (p = 0.003) and biparietal diameter 2.97 ± 0.30 vs 3.04 ± 0.27 (p = 0.043) compared to with neonates with normal outcome , and between the abdominal circumference velocity and a neonate with NICU stay, . There was no significant association between the abdominal circumference velocity and neonatal hospital stay, , metabolic acidosis,  and APGAR at 5 min < 5, . All associations were corrected for maternal age, BMI and parity.There was an inverse association between the abdominal circumference velocity and a composite adverse neonatal outcome (−odds ratio (OR) = 0.667 , more NICU stays  and more hospital admissions , compared to neonates who had a higher than average birth weight despite a below average AC at 20 weeks (birth weight ≥ expected) , suggesting a late reduction in growth velocity had significantly more composite adverse neonatal outcomes  (birth weight centiles between 10 and 80) in relation to their antenatal growth velocities. We aimed at identifying a subgroup within AGA neonates with reduced growth velocity, but who were not classified as small or growth restricted as their birth weight was above the 10th centile according to the Dutch perinatal registry system. In this study, these AGA neonates with suboptimal birth weight (arbitrarily defined as birth weight p10–50) had reduced velocities of all fetal growth parameters compared to the optimal AGA reference group (birth weight p50–80). Although we could not detect significant differences in neonatal outcomes based on birth weight categories, neonates with a composite adverse neonatal outcome and NICU stay had significantly lower growth velocities in the abdominal circumference, head circumference and biparietal diameter velocity compared with healthy neonates. These data suggest that abnormal fetal growth velocities are associated with adverse neonatal outcomes of presumed appropriate-for-gestational-age neonates due to suboptimal fetal growth.Strengths of this study were the large sample size and the comprehensive registration of ultrasound, obstetric and neonatal parameters in a single tertiary centre. Another strength of this study is the introduction of a new and practical method of assessing fetal growth potential within the AGA group using a simple calculation that can be readily employed and interpreted in low-resource setting without the need of complex mathematical models. An important limitation of the study is the retrospective design, with the inherent risk of selection bias and the exclusion of many cases in which the ultrasound examination did not fall within the specified time periods. Another limitation is the heterogeneity of the study population with various risk profiles for IUGR, as the study was performed in a tertiary referral centre. There was inadequate recording of determinants of obstetric risk and other confounders (such as ethnicity) to enable post-hoc stratification. This might limit the interpretation of our data and the generalizability to an unselected low-risk population. Caution must also be taken in interpreting our data as the association of fetal growth velocities with neonatal birthweight and adverse outcome does not necessarily imply the ability of such ultrasound parameters to identify individuals at risk for adverse outcomes. The degree of overlap in the min-max range of these velocities between normal and abnormal groups, especially in a large sample as in this study, weakens the predictive power of such parameters .Undiagnosed fetal growth restriction is recognized as a major contributor to stillbirths and perinatal morbidity , 25. TraDetermining optimum fetal growth is the cornerstone of proposing strategies for antenatal prediction and surveillance of pregnancies at risk of fetal growth restriction. Alas, this is an intricate and complex concept with competing and interacting influences from genetic, epigenetic and environmental backgrounds . SeveralThis study highlights the importance of performing a third trimester biometry scan in an unselected population to determine target fetal growth. In the Netherlands, third trimester biometry scans are scheduled only for women who are at high risk of fetal growth restriction, according to national guidelines and agreements between gynaecologists and primary care midwives. There is ample evidence suggesting that the detection rate of small-for-gestational age improves with the additional scan in the third trimester  and tripIn conclusion, neonates with ‘appropriate’ birth weight for gestational age are a heterogeneous population, that includes a small ‘at risk’ group of fetuses who failed to reach their growth potential. How to tease out these apparently normal grown but ‘relatively small for gestational age’ fetus is a major challenge. Measuring abdominal circumference growth velocity in the third trimester, in combination with fetal dopplers and biomarkers of placenta function, could improve the identification of at risk fetus and are potential candidates for inclusion in multivariate models predicting fetal growth restriction.


To evaluate the association between hematological parameters at birth and the risk of moderate-severe bronchopulmonary dysplasia (BPD) in a cohort of extremely preterm infants.This is a retrospective study of all extremely premature infants admitted to the neonatal intensive care unit, Shenzhen Maternity and Child Healthcare Hospital from January 2016 to May 2018. Extremely prematurity was defined as a delivery at a gestational age ≤ 28 weeks or a birth weight ≤ 1000 g. BPD was diagnosed if oxygen exposure exceeded 28 days and the severity was decided at 36 weeks PMA or discharge. Multivariable analysis was performed to assess the independence of the association between hematological parameters at birth and risk of moderate or severe BPD.9/l, P = 0.004; 5.0 vs 2.95*109/l, P = 0.023; 0.88 vs 0.63*109/l, P = 0.026, respectively) whereas the mean platelet volume was significantly lower in infants with moderate-severe BPD than those without BPD . After adjusting for covariates, the risk of moderate-severe BPD was independently associated with platelet count≥207*109/l .A total of 115 extremely premature infants were analyzed in this study. The median platelet count, neutrophil and monocyte count at birth were significantly higher in infants with moderate-severe BPD compared to infants without BPD (228 vs 194*10Our findings suggest that hematologic parameters at birth are different in extremely preterm infants who will develop moderate-severe BPD. A higher platelet count at birth may increase the risk of moderate-severe BPD after extremely premature birth. Bronchopulmonary dysplasia (BPD) affects around 50% of extremely preterm infants , 2. OverThe pathogenesis of BPD is largely attributed to the arrested lung development in these extreme preemies . Gestatiet. al and F. Cekmez et. al both reported a high level of mean platelet volume (MPV) in the first days of life is associated with increased risk of BPD in preterm infants . The Shapiro-Wilk test was used to evaluate the normality of continuous variables. Unpaired t test or Mann-Whitney U test was adopted to analyze continuous variables, as appropriate. Chi-square or Fisher’s exact test were used to compare categorical data, as appropriate. Multivariate logistic regression was performed to determine the independent risk factors of moderate or severe BPD. The odds ratios (OR) and 95% confidence interval (CI) were calculated in logistic regression analysis. Afterwards, receiver-operator curve (ROC) was applied to calculate the cut-off values to dichotomize the corresponding continuous variables significantly related to the occurrence of moderate or severe BPD in multivariate logistic regression analysis. Finally, univariable logistic regression model was built to find the independent risk factors for the occurrence of moderate or severe BPD and its related morbidities.The Shenzhen Maternity and Child Healthcare Hospital Institutional Ethical Committee (IEC) approved the collection and usage of the clinical information for research purposes and waived the requirement for informed consent (IEC No. [2018]-082).A total of 318 extremely premature infants were admitted to our NICU during the study period. Diagnosis of BPD was made in 166 (75%) infants in which 106 (48%) infants were categorized as mild BPD and 60 (27%) as moderate-severe BPD , intubation at resuscitation (88% vs 45%), mechanical ventilation (85% vs 40%), (suspected) early onset neonatal sepsis 43% vs 16%), PDA (58% vs 18%) and surfactant treatment . The mean platelet volume (MPV), basophil percentage and lymphocyte percentage were significantly lower infants with moderate or severe BPD compared with no BPD infants .The comparison of hematologic parameters at birth between infants without BPD and with moderate or severe BPD was displayed in Table P = 0.032), PDA , (suspected) early-onset neonatal sepsis  and platelet count , sensitivity (0.717), specificity (0.600) and Youden index (0.317). The clinical outcome of this cohort was stratified by the platelet count (Table 9/l at birth was slightly longer compared with infants with platelet count ≤207 *109/l at birth (89 (IQR: 62–120) vs 71 (IQR: 50–99), P = 0.048).Receiver-operator curve was applied to calculate the cut-off value of the significant continuous variables optimally assessing the risk moderate-severe BPD Fig. . A platent Table . BesidesThe present study systematically analyzed the hematologic parameters at birth in a cohort of extremely premature infants and further evaluated the association between these features and the risk of moderate or severe BPD. We found that the platelet counts at birth were significantly higher in infants developing to moderate-severe BPD in later life. In addition to the well-known risk factors like intubation at resuscitation, PDA and (suspected) early-onset neonatal sepsis, this study showed that platelet count at birth was also an independent risk factor for the occurrence of moderate-severe BPD. Gestational age, may be owing to the population characters, was identified as a non-independent risk factor.et. al found low neutrophil count (< 1*109/l) predicted the BPD severity level  in very low birth weight (VLBW) infants [9/l was only detected in 5 infants without BPD and 6 infants with moderate-severe BPD. This discrepancy may thus be attributed to the small sample size in current study. Large studies are needed to validate the predictability of neutrophil count at birth for the risk of BPD.BPD is a severe complication that leads to increased short- and/or long-term morbidity and mortality. Several hematologic parameters during the first days of life are related to the increased risk of BPD. Palta, M  infants , which iet. al found that MPV > 11 fl at 24–48 h after birth in infants born earlier than 30 weeks was associated with the occurrence of moderate and severe BPD whereas the MPV and platelet count at birth were comparable in infants with and without moderate-severe BPD [et.al also found an increased MPV in the first days of life was associated with the development of BPD group in infants born < 34 weeks or with birth weight < 1500 g [The association of MPV with the risk of BPD was reported in several studies , 12. Danvere BPD . Cekmez It is interesting that the platelet counts at birth was associated with the occurrence of moderate-severe BPD. However, the underlying mechanisms remains to be elucidated. Pulmonary inflammation plays a pivotal role in the arrested lung development following extremely preterm birth , 5. In aA newborn’s platelet count can be influenced by several factors. Infection and inflammation may increase the platelet shortly and then consume a lot. Antibodies generated by maternal immune system under some pathologic condition may also enter the fetal circulation, attack the platelet and lead to decreased platelet count in newborn . In currThe main strength of our study is the great applicability in routine practice. BPD remains a major challenge for perinatologists. The accurate and rapid identification of high-risk infants is of paramount importance for the prevention of BPD. However, our data should be interpreted with care. Besides of the retrospective design, an inclusion bias in our study has incurred because we excluded the infants who died before the diagnosis of BPD was made. These infants may be also at increased risk of moderate or severe BPD due to the intubation in most cases prior to death. Moreover, the cut-off value of hematologic parameters at birth was calculated in a relatively small cohort of extremely preterm infants. Large prospective studies are required to confirm the findings in this study. The function of the platelet was not measured in this manuscript. Besides, it would be interesting to have a look at the continuous platelet count in the first week of life and its predictive value for BPD.9/l at birth is an independent predictor for the occurrence of moderate-severe BPD.In conclusion, hematologic parameters at birth are different in extremely preterm infants with moderate-severe BPD. A platelet count > 207*10


To describe cystoid macular degeneration (CMD), which has no clear definition in diabetic macular edema (DME), and examine its features in optical coherence tomography (OCT) and fundus fluorescein angiography (FFA).This study was conducted using OCT images of patients who were followed in Gazi University between November 2011 and March 2015. A total of 259 eyes (187 patients) found to have cystic changes on OCT were included. Macular ischemia, peripheral ischemia, and type of edema were identified on FFA. Vitreomacular interface abnormalities, foveal contour integrity, internal reflectivity of the cysts, and outer retinal layer defects were analyzed from OCT images. The horizontal and vertical diameters of the largest cyst within 1000 μm of the foveal center were measured for the definition of CMD. Cut-offs for these values were determined by receiver operating characteristic curve analysis. Cystoid macular edema (CME) and CMD groups were created and their characteristics were analyzed.The horizontal and vertical diameters of the largest cyst were moderately positively correlated with visual acuity . Eyes with horizontal diameter of the largest cyst ≥450 μm were classified as CMD; in this group, sensitivity in the prediction of visual acuity ≤20/60 was 58%. Eyes with horizontal diameter of the largest cyst <450 μm were classified as CME; in this group, specificity in the prediction of visual acuity >20/60 was 73%. For the threshold of 300 μm determined for vertical diameter of the largest cyst, sensitivity was 62% and specificity was 69%. The CME and CMD groups were formed according to these cut-off values. Compared to the CME group, the CMD group had greater central subfield thickness and higher prevalence of outer retinal damage, severe disruption of foveal contour, macular ischemia, and diffuse/mixed type edema.In eyes with DME, CMD can be defined as the largest cyst within 1000 μm of the foveal center having a horizontal diameter of ≥450 μm and vertical diameter ≥300 μm, especially if associated with macular ischemia, outer retinal damage, loss of foveal contour, and diffuse/mixed type edema. Although Otani et al.3 defined CME as hyporeflective spaces separated by hyperreflective septa, there is no quantitative value for the cyst diameters when defining CME in the hitherto literature.Diabetic macular edema (DME) is the most common cause of visual deterioration in diabetic retinopathy (DR).4 CMD was seen to develop after CME with associated photoreceptor cell loss.4 CMD was also defined in chronic central serous chorioretinopathy (CSCR) as cystoid spaces in optical coherence tomography (OCT) with no fluorescein leakage.5 This term was always related with poorer visual acuity.6 In age-related macular degeneration (AMD), CMD was also defined as the presence of degenerated pseudocyst or retinal degeneration that had intraretinal cystic spaces.7 However, it is important to differentiate between CME and CMD in AMD because degenerative cysts are not an indicator of the activity of the lesion.Another definition used between clinicians is cystoid macular degeneration (CMD). CMD was first defined in chronic retinal vein occlusion, in a histopathological experimental study.The aim of this study was to define and characterize CMD in DME, for which there is no clear definition. CMD is thought to be the result of chronic edema and may be associated with an unfavorable visual outcome. Determination of DME characteristics is necessary to predict visual prognosis and select appropriate treatment.In this retrospective cross-sectional study, an evaluation was made of 398 OCT scans of the eyes of 223 patients who were followed up with the diagnosis of DME at Gazi University Department of Ophthalmology between November 2011 and March 2015. A total of 259 eyes of 187 patients  who met the inclusion criteria were included in the study. The study was approved by the Local Ethics Committee of Gazi University.Eyes with clinically significant macular edema as defined by ETDRS, that had fundus fluorescein angiography (FFA) and high-quality spectral OCT were included in the study. If the patient had received any prior treatment, OCT images obtained at least 3 months after the last treatment  were included in the study. Eyes with visually significant cataract or any other pathology causing visual deterioration such as corneal opacity, significant vitreous hemorrhage, optic atrophy, amblyopia, macular edema due to other causes such as uveitis, retinal vein occlusion and concurrent macular degeneration, or macular hole were excluded from the study. Eyes which had undergone cataract surgery within the last 6 months were also excluded from the study to exclude Irvine-Gass syndrome.The demographic features of the patients  and stage and duration of DR were recorded. Best corrected visual acuity (BCVA) measured with Snellen chart, fundus examination, OCT, and FFA images were evaluated. BCVA was converted to LogMAR for statistical analysis. All OCT scans and FFA investigations were performed with Heidelberg Spectralis OCT .8Macular ischemia and type of edema were noted from FFA images. Macular ischemia was defined as an enlarged foveal avascular zone (≥1000 µm) or capillary non-perfusion areas within one disc diameter distance of the foveal center.10Edema was classified as focal, diffuse, or mixed type. Focal edema was defined as local leakage areas with well-defined borders, and the term diffuse edema was used when large, poorly defined leakage areas affected the fovea. If there were features of both types of leakage, the edema was defined as mixed type.11 In qualitative analysis of OCT scans, the presence of intraretinal cystic changes, serous foveal detachment (SFD), vitreomacular interface (VMI) abnormalities, outer retinal layer defects , integrity of the foveal contour, and internal reflectivity of the cysts were evaluated. Cystic changes were defined as round or oval areas of low reflectivity separated by hyperreflective septa.3 SFD was defined as shallow elevation of the posterior surface of the retina appearing as optically clear, dome-shaped areas between the neurosensorial retina and RPE on OCT scans.13Central subfield thickness (CSFT), defined as the average thickness in the central 1000 µm-diameter circle of the ETDRS grid in OCT, was used for quantitative analysis of DME.14VMI abnormalities were evaluated in six groups, with modifications made to the classification of the International Vitreomacular Traction Study group.1. Total perifoveal detachment: Posterior vitreous surface is completely detached from the macular region but not from the optic disc as seen in OCT2. Vitreomacular adhesion (VMA):a) Focal VMA (area of adhesion ≤1500 µm)b) Broad VMA (area of adhesion >1500 µm)3. Epiretinal membrane4. Vitreomacular traction (VMT):a) Focal VMT (area of traction ≤1500 µm)b) Broad VMT (area of traction >1500 µm)15Outer retinal layer defect was defined as a loss of continuity of either the ELM or IS/OS band in the central 0.1 mm of the fovea. Shadowing behind the cysts and hard exudates were separated carefully.Integrity of the foveal contour was evaluated in three groups: 1) normal foveal depression; 2) normal foveal depression was disturbed but had not disappeared completely (mild distortion), 3) the foveal depression was completely flat or elevated (severe distortion).16Internal reflectivity of the cysts was classified as hyporeflective if similar to the vitreous, isoreflective if similar to the retinal layers, or heterogeneous (as defined in an earlier study).The largest cystoid space was determined for each eye and the horizontal and vertical diameters of the largest cyst in the area within 1000 µm of the foveal center were noted. All measurements were performed by the same investigator (N.G.Y.) using a manual caliper . To ensu17 The relationship between BCVA and the horizontal and vertical diameters of the largest cyst resulting in severe visual loss was evaluated with receiver operating characteristic (ROC) analyses.The minimum BCVA to read newspaper print is known to be 20/60 (Snellen), and BCVA <20/60 is defined as severe visual loss.Cut-off values to differentiate the CME and CMD groups were determined from this analysis. The CME and CMD groups were created and the defined OCT and FFA findings were analyzed in the groups to determine the features of CMD.Data obtained from the study were recorded using Excel for Windows  and statistical analyses were performed using the Statistical Package for the Social Sciences for Windows . The statistical level of significance was set to p<0.05. The Kolmogorov-Smirnov test, histograms, and P-P plots were used for the continuous variables to test the conformity to normal distribution. For comparisons of two groups, the independent samples t-test or Mann-Whitney U test were used according to the normality result. One-way ANOVA and LSD test for post-hoc analyses were used for comparisons of three or more groups if the variables were normally distributed, and the Kruskal-Wallis test was used if the variables were not normally distributed. The Mann-Whitney U test with Bonferroni correction was used for post-hoc analysis if the result revealed a significant difference. In correlation analysis, Pearson or Spearman correlation test were used according to the normality result. Pearson chi-square or Yate’s corrected chi-square tests were used for categorical variables. ROC curve analysis was used for the predictive value of the horizontal and vertical diameters of the largest cyst for severe visual loss.A total of 259 eyes of 187 patients (49.2% women and 50.8% men) met the inclusion criteria. DME was detected in 138 right eyes (53.3%) and 121 left eyes (46.7%). There were 72 patients (38.5%) with bilateral involvement and 115 patients (61.5%) with unilateral DME. Other demographic features of the cases are shown in The mean CSFT was 474±131 (254-1121) µm. Cystic changes were detected in most cases . Therefore, the final analysis of the study was made in these 251 eyes. The horizontal diameter of the largest cyst did not conform to normal distribution while the vertical diameter of the largest cyst showed normal distribution. The median of the horizontal diameter was 433 (126-2213) µm and the mean of the vertical diameter was 305±142 (77-1059) µm.s=0.349; p<0.001, s=0.487; p<0.001, s=0.798; p<0.001, s=0.678; p<0.001, The correlation between the horizontal and vertical diameters of the largest cyst and BCVA showed weak to moderate positive correlation  and those with <450 µm were classified as CME (CME-H group), while eyes with vertical diameter of the largest cyst ≥300 µm and <300 µm were classified as CMD (CMD-V group) and CME (CME-V group), respectively.OCT and FFA parameters related to these CME and CMD groups are shown in 7The definition of CMD was previously made for CSCR and AMD, but there has been no reported definition in DME. It is important to define CMD and identify the related features to have more information about the prognosis of edema and the benefit of treatment. It has been associated with poor visual acuity in CSCR, and is said to affect the need for treatment in AMD.18 In the chronic stage, fluid accumulates intracellularly. The subsequent death of Müller cells and neuroglia results in the formation of large cystoid cavities.19 Otani et al.3 reported the acute and chronic morphologies of DME in an OCT-based study and stated that the disappearance of septa resulted in confluent large cysts which might fill all layers of the retina. Consistent with this pathogenesis, Yamomoto et al.20 found that eyes with CME had lower visual acuities than other types in OCT. In light of these data, it can be considered that in the chronic phase of cyst formation, the horizontal diameter of the cyst enlarges, damaging the adjacent retina. This data formed the basis of this study to define CMD. Also, Das et al.18 showed that eyes which had cystic changes with septa had higher visual acuity values than eyes which had nonseptated cystic spaces.Cyst formation begins with intercellular fluid accumulation. Coalescence of the extracellular fluid occurs due to the disruption of Müller cells, whose pump-like function keeps the macula dry.21 The results of that study showed a moderate degree of correlation between the horizontal diameter of the largest cyst and visual acuity (LogMAR). This was encouragement for further analysis. Similarly, a moderate degree of correlation was determined between the vertical diameter of the largest cyst and visual acuity (LogMAR) . The high correlation of the two diameters of the cyst can be interpreted as enlargement of the cyst in these two planes. In a previous study, height of the foveal cystoid space and inferior subfield retinal thickness were found to be correlated.22 Retinal thickening in the inferior quadrant in particular was interpreted as a result of the disrupted retinal integrity with long-term cystic changes and the accumulation of fluid in the inferior zone due to gravity.23 Consistent with these findings and relationships, we believe that cystoid degeneration occurs due to increased cystic changes in both the horizontal and vertical planes in prolonged edema.The baseline characteristics of our study, such as mean age and male predominance, were similar to the TURK-DEM study, which reflected the overall DME patients in Turkey.s=0.798). Also, a moderate correlation between the horizontal diameter of the largest cyst and CSFT was observed (correlation coefficient rs= 0.487). Large cysts tend to form in the foveal region, which has no inner retinal layers.25 At the center of the fovea, where there are no inner layers, the retina is more vulnerable to the development of large cysts and increases in mechanical stresses when the axial expansion of cysts is not sufficient to compensate for the increased volume.26 In light of this pathogenesis and the findings of the current study, we hypothesize that cyst enlargement continues in the horizontal plane after the vertical expansion exceeds the capacity of the retina. This process occurs with the degeneration of the retina.As expected, there was medium to high correlation between the vertical diameter of the largest cyst and CSFT , refers to the disruption of the bipolar, horizontal, and amacrine cell synaptic field. Consequently, transmission between photoreceptors and ganglion cell complex is impaired.29 DRIL was found to be responsive to anti-vascular endothelial growth factor therapy.31 Yohannan et al.32 reported that the presence of a cyst is associated with decreased retinal sensitivity independent of increased retinal thickness and IS/OS junction disruption.In some previously published studies, it has been suggested that cysts have a damaging effect on bipolar and ganglion cells.33 In another study, Koleva-Georgieva and Sivkova34 showed a negative correlation between BCVA and cystoid DME groups . In the hitherto literature there is no reported definition of CME according to cyst size with a specific cut-off value using OCT. In the current study, it was also aimed to find a cut-off value to distinguish CMD from CME. With this finding, the starting point of the degenerative effect of a cyst can be determined. In the current study, the horizontal and vertical diameters of the largest cyst were higher in cases with outer retinal damage, macular ischemia, and diffuse or mixed edema. These conditions are known to be associated with poor visual prognosis.46The presence of macular cystoid spaces has been found to be predictive of reduction in BCVA, and larger cystoid spaces were found to be more disruptive than small ones in a previous study by Sophie et al.In this study, CME and CMD groups were formed according to the horizontal and vertical diameters of the largest cyst. Horizontal cyst diameter ≥450 µm was defined as CMD. In this group, sensitivity was 58% for the prediction of visual acuity <20/60. In other words, eyes with horizontal cyst diameter ≥450 µm had a 58% probability of visual acuity <20/60. Horizontal cyst diameter <450 µm was defined as CME and had 73% specificity for the prediction of visual acuity ≥20/60. Therefore, eyes with horizontal cyst diameter <450 µm had 73% probability of visual acuity ≥20/60. Vertical cyst diameter ≥300 µm was defined as CMD. In eyes with vertical cyst diameter ≥300 µm, the probability of visual acuity <20/60 (sensitivity) was 62%. Vertical cyst diameter <300 µm was defined as CME, and the probability of visual acuity ≥20/60 (specificity) was 69% in this group.47 In addition, the occurrence of cystoid spaces in the capillary nonperfusion areas and lack of reperfusion of these areas after the resolution of the chronic cystoid edema was shown in a previous OCT angiography study.48 The findings of the current study, which showed that more degeneration findings are present in ischemic cases, supported these data.A higher rate of outer retinal damage was observed in the CMD groups than in the CME groups. Likewise, macular ischemia was detected at a higher rate in the CMD groups than in the CME groups. Degeneration and macular ischemia seem to be related processes. In a previously published study, vascular hyperpermeability and ischemia were shown to cause necrosis and apoptosis in the neuroglia cells and this process resulted in large cystoid cavities. A vicious circle ensues with the enlargement of the cystoid spaces causing enlargement of the foveal avascular zone and increased foveal ischemia.49 evaluated foveal contour integrity in various ocular diseases, the current study is the first to use this parameter for grouping and analysis in DME to define CMD.In the current study, the integrity of the foveal contour was also studied with an expectation that the presence of normal foveal contour or mild distortion were more likely to be associated with CME groups and severe distortion with the CMD groups. Indeed, our results showed that severe distortion of the foveal contour was more prevalent in CMD groups. Although Jun et al.16 showed that accumulations in a cyst isoreflective to the plexiform layer were associated with fibrin and inflammatory debris. The heterogeneous reflectivity group of our study refers to this finding. Higher reflectivity of cystoid spaces was observed by Barthelmes et al.50 in exudative diseases such as DME compared to the normal vitreous and cystic spaces in degenerative diseases.In a previous study, Liang et al.51 Contradictory to our hypothesis, the mean density of cystoid spaces was found to be negatively correlated with retinal sensitivity.52 Further studies are needed to clarify the relationship between the reflectivity of cystoid spaces and the degeneration process.Although there was no supporting finding in our study, we hypothesize that the internal reflectivity of the cysts was related with chronicity and degeneration. Initially, the cyst is usually isoreflective. Then, cyst reflectivity becomes heterogeneous on OCT due to the debris accumulation as a result of degeneration. The degenerated cyst becomes hyporeflective in the chronic stage. In an earlier study supporting our hypothesis, the optical intensity of the cystoid space was thought to be a finding indicating chronicity.To the best of our knowledge, this is the first study to determine characteristics of CMD in DME. With these findings, degenerative cases can be diagnosed early in the management of DME. There were some limitations of this study. One is the retrospective design, and another is that there was no follow-up or evaluation of the treatment which was administered. The interpretation of some data such as foveal contour may contain bias. This subjective evaluation can be considered one of the limitations of the study. Future prospective studies investigating treatment response in eyes with CMD with follow-up information would be helpful to predict eyes with poor visual prognosis (such as those with CMD) and eyes with CME, which probably have better prognosis.In conclusion, cystoid degeneration in DME can be defined as the largest cyst in the central fovea having a horizontal diameter >450 µm and vertical diameter >300 µm, especially with concomitant macular ischemia, outer retinal damage, loss of foveal contour, and diffuse/mixed edema subtype. This definition can provide a new perspective to professionals in patient assessment and may help estimate the benefit of treatment.