1295School age outcomes in IVF-conceived children compared with controls: a population linkage study

Background There is interest in longer term outcomes in IVF-conceived offspring compared with those conceived naturally. So far, the findings have been conflicting. The Australian Early Developmental Consensus (AEDC) assesses children in their first year of primary school across five domains. Methods To compare school entry outcomes in IVF-conceived children with naturally conceived controls, we undertook a statewide data linkage study, with perinatal data (2005-2014) linked to data from IVF providers in Victoria and the AEDC. Our approach to analysis included: complete case analysis, multiple imputation of missing data, consideration of clustering (siblings) and inverse probability weighted modeling to adjust for covariates. Our primary outcome was an AEDC score indicative of developmental vulnerability in two or more domains. We adjusted for confounders: child’s age at assessment, sex, highest level of maternal education, maternal age, parity, SEIFA (Socio-Economic Indexes for Areas) quintile, language background other than English, and Aboriginal and Torres Strait Islander (ATSI) status. Results The linked dataset comprised 163,418 children, including 4,441 IVF-conceived children. The IVF-conceived population had older, more highly educated mothers who lived in more affluent areas and were less likely to be from non-English speaking backgrounds or identify as ATSI. IVF-conceived children were less likely to be developmentally vulnerable, in both unadjusted (RR 0.59, 95%CI:0.52-0.67, p < 0.001) and adjusted analyses (aRR 0.72, 95%CI:0.58-0.88, p < 0.001). Conclusions IVF-conceived were less likely to be developmentally vulnerable in their first year of schooling, compared with peers conceived naturally.

Perinatal Data of Refugee Women from the Gynaecology Department of Charité University Hospital Berlin Compared with German Federal Analysis

Introduction The aim of this study was to record the perinatal data of refugee women at Charité Hospital, Berlin, and to evaluate possible differences in pre-, peri- and postnatal outcomes compared with indigenous women. Material and Methods All pregnant women who gave birth in the period from 1 January 2014 to 30 September 2017 and were registered at least once in the hospital as “refugee” were included in the analysis. The data recorded from the refugee women were compared with the perinatal data of the German Federal obstetric analysis for the year 2016, which was published by the IQTIG (Institut für Qualitätssicherung und Transparenz im Gesundheitswesen [Institute for Quality Assurance and Transparency in Healthcare]). Results The analysis comprised 907 refugee women and 928 infants (21 twin pregnancies). Pregnant refugee women were significantly younger than the pregnant women from the Federal analysis (birth before the age of 30: 66 vs. 41%, p < 0.001, RR: 1.6, 95% CI: 62.9 – 69.2). They had a history both of more pregnancies (≥ 3 pregnancies: 29.4 vs. 13.4%, p < 0.001, RR: 2.2, 95% CI: 26.4 – 32.5) and of more miscarriages (> 2 miscarriages: 9.7 vs. 5.9%, p < 0.001, RR: 1.6, 95% CI: 7.9 – 11.8) and more often had a history of suffering from psychological stress (11.1 vs. 4.1%, p < 0.001, RR: 2.70, 95% CI: 9.2 – 13.4). There were more premature births (10.3 vs. 3.0%, p < 0.001, RR: 3.36, 95% CI: 8.4 – 12.4), post-term pregnancies (8.5 vs. 0.5%, p < 0.001, RR: 15.4, 95% CI: 6.7 – 10.5), and cases of postpartum anaemia (28.7 vs. 22.0%, p < 0.001, RR: 1.30, 95% CI: 25.7 – 31.7) and puerperal endometritis (1 vs. 0.2%, p = 0.006, RR: 4.3, 95% CI: 0.5 – 1.9) compared with the Federal analysis. The neonatal outcome showed an increased rate of hypotrophy (11 vs. 7%, p < 0.001, RR: 1.6, 95% CI: 9.1 – 13.2), more stillbirths (0.7 vs. 0.2%, p = 0.006, RR: 3, 95% CI: 0.2 – 1.4) and increased congenital malformations (2.8 vs. 0.4%, p < 0.001, RR: 3, 95% CI: 0.2 – 1.4). Conclusion Both refugee women and their infants showed significant differences. Despite the average younger age of the pregnant refugee women, the rates of premature birth and stillbirth and congenital malformations were significantly more frequent. More intensive antenatal screening with differentiated foetal organ diagnostics including psychosomatic care could contribute to early identification and prompt diagnosis. As regards the postpartum anaemia and puerperal endometritis, which occur more often in refugee women, midwife engagement and an improvement in the living situation in homes and accommodation facilities could be of great importance.

Process variations between Swiss units treating neonates with hypoxic-ischemic encephalopathy and their effect on short-term outcome

Objective To compare therapeutic hypothermia (TH) treatment of term and near-term neonates with hypoxic-ischemic encephalopathy (HIE) between neonatal units. Study design Population-based, retrospective analysis of TH initiation and maintenance, and of diagnostic imaging. The comparison between units was based on crude data analysis, indirect standardization, and adjusted logistic regression. Results TH was provided to 570 neonates with HIE between 2011 and 2018 in 10 Swiss units. We excluded 121 off-protocol cooled neonates to avoid selection bias. Of the remaining 449 neonates, the outcome was favorable to international benchmarks, but there were large unit-to-unit variations in baseline perinatal data and TH management. A total of 5% neonates did not reach target temperature within 7 h (3–10% between units), and 29% experienced over- or undercooling (0–38%). Conclusion Although the neonates had favorable short-term outcomes, areas for improvement remain for Swiss units in both process and outcome measures.

P–763 Neonatal outcomes of the first 65 infants delivered after IVF treatment with progestin-primed ovarian stimulation using dienogest in patients with endometriosis

Study question What is the perinatal outcome of pregnancies resulting from a controlled ovarian hyperstimulation (COH) regimen of progestin-primed ovarian stimulation (PPOS) protocol using dienogest (DNG) in patients with endometriosis? Summary answer No difference in mean birth weight, however preterm and low birth weight babies are significantly more in the group treated with PPOS using DNG. What is known already Dienogest is an oral progestin effective for the treatment of endometriosis, such as reduction of endometrial lesion and control of pain intensity with safety profile and good tolerability. We reported for the first time in the world that DNG was better than dydrogesterone (DYG) for PPOS in terms of the mature oocytes rate and the fertilization rate in patients with endometriosis. Although there have been several reports of infants born with PPOS using DYG, it is essential to report on the perinatal outcome of embryos transferred after treatment with PPOS using DNG from now on. Study design, size, duration: We prospectively investigated the perinatal outcomes of 65 newborns which were the result of using a new COH regimen; PPOS with DNG. The results were compared with perinatal outcome data of babies born between 2018 and 2020 to 815 patients who underwent assisted reproductive technology (ART) treatment at our fertility center. As for the congenital malformation rate, the data was also compared with the 2017 Japanese data bank of babies born after ART treatment. Participants/materials, setting, methods We studied the perinatal data of all babies born after transfer of frozen embryos acquired by COH using PPOS protocol with DNG. The rate of maternal complications during pregnancy, pregnancy duration, birth weight, congenital malformations and method of delivery were investigated. We compared the perinatal outcomes of infants born after in vitro fertilization (IVF) and frozen embryo transfer at our center during the same period. Main results and the role of chance Perinatal data of 65 babies (study group) were compared with the perinatal data of 840 babies born after IVF at our center, and 47807 babies born after ART in Japan, 2017. We found 3 twin and 59 singleton pregnancies in the study group, compared to 23 twins, 1 triplet and 791 singleton pregnancies during the same period at our center. Considering singletons, there was no difference in mean birthweight (study group; 2893.2±652g vs. total at our center; 3001.2±425g, respectively, p = 0.102). Preterm births (&lt;37 weeks) were significantly more frequent in the PPOS using DNG treatment group than in total at our center (19.2% vs. 9.7%, p = 0.016). The percentage of infants with a birth weight &lt; 2.5 kg was also significantly higher in the PPOS treatment group compared to the total at our center (22.6% vs.11.9%, p = 0.015). The Caesarean section rate was 53.2% in the study group vs. 47.1% control group of our center respectively (p = 0.353). One babies in the study group had malformations in the ocular region. There was no significant difference in congenital malformations between the study group and ART data bank in Japan, 2017 (OR 0.67, 95% CI 0.093: 4.836). Limitations, reasons for caution The number of babies is still low, further prospective studies including larger populations are needed to confirm the efficacy of PPOS protocol with DNG. Wider implications of the findings: This is the first report on the perinatal outcome of babies born by a new COH method using PPOS with DNG, which is a combination of endometriosis treatment and COH for IVF. The association of endometriosis with preterm birth and low birth weight needs to be further investigated. Trial registration number UMIN000031111

Changes in Neonatal Morbidity and Neonatal Care Practices of Infants Born Very Preterm in the Netherlands in the 1980s and 2000s

This study evaluates changes in neonatal morbidity and care practices of very preterm (VP) infants born in the Netherlands in the 1980s and 2000s and analyzes whether these changes were associated with infant and maternal characteristics, risk factors during pregnancy, and obstetrical outcomes.The community-based cohorts of POPS (1983) and LOLLIPOP (2002-03) provided perinatal data for the study. The analysis enrolled 1,228 participants born VP (before 32 weeks of gestation) and survived to 2 years of age. In 2003, mothers were on average 3.3 years older when giving birth than in 1983. Multiple birth rates increased by 50% and significantly more parents had higher education. Prevalence of severe IVH and sepsis decreased in VP infants between 1983 and 2003. LOLLIPOP infants received more often continuous positive airway pressure (CPAP), mechanical ventilation, and caffeine therapy than POPS infants. Antenatal corticosteroids and surfactant therapy were introduced only in the LOLLIPOP cohort. In 2002-03, length of stay in the NICU was reduced by 57% in LOLLIPOP (median 16 days) compared to POPS (median 38 days). LOLLIPOP infants also spent 11 days less total time in hospital after birth (median 54 days). This is a reduction of 17% compared to POPS (median 65 days). Differences persisted after adjustment for infant and maternal characteristics, risk factors during pregnancy, and obstetrical outcomes.Conclusions: Infant and mother characteristics changed considerably as well as obstetric and neonatal care practices. Outcomes of several severe neonatal morbidities improved. Length of NICU and hospital stay were significantly shorter in the 2000s.

The Association between the Five-Minute Apgar Score and Neurodevelopmental Outcomes among Children Aged 8−66 Months in Australia

This study aimed to evaluate the association of the five-minute Apgar score and neurodevelopmental outcomes in children by taking the entire range of Apgar scores into account. Data from the Australian Longitudinal Study of Women’s Health (ALSWH) and Mothers and their Children’s Health (MatCH) study were linked with Australian state-based Perinatal Data Collections (PDCs) for 809 children aged 8−66 months old. Generalized estimating equations were used to model the association between the five-minute Apgar scores and neurodevelopmental outcomes, using STATA software V.15. Of the 809 children, 614 (75.3%) had a five-minute Apgar score of 9, and 130 (16.1%) had an Apgar score of 10. Approximately 1.9% and 6.2% had Apgar scores of 0−6 and 7−8, respectively. Sixty-nine (8.5%) of children had a neurodevelopmental delay. Children with an Apgar score of 0−6 (AOR = 5.7; 95% CI: 1.2, 27.8) and 7−8 (AOR = 4.1; 95% CI: 1.2, 14.1) had greater odds of gross-motor neurodevelopment delay compared to children with an Apgar score of 10. Further, when continuously modelled, the five-minute Apgar score was inversely associated with neurodevelopmental delay (AOR = 0.75; 95% CI: 0.60, 0.93). Five-minute Apgar score was independently and inversely associated with a neurodevelopmental delay, and the risks were higher even within an Apgar score of 7−8. Hence, the Apgar score may need to be taken into account when evaluating neurodevelopmental outcomes in children.

Serum Melatonin as a Biomarker for Assessment of Late-term and Postterm Pregnancies in Women without Spontaneous Onset of Labor

We conducted a prospective study to assess serum melatonin as a biomarker to predict the development of late-term and postterm pregnancies and spontaneous beginning of labor in women with term pregnancies. Population of this prospective study included pregnant women with late-term and postterm pregnancies and term pregnancies as controls. In these study groups, serum melatonin concentrations were measured in women with or without labor and their perinatal data were collected. In the postterm pregnancies without labor, the lowest median melatonin concentrations were measured (p<0.05). In the late-term and postterm pregnancies with and without labor, the median serum melatonin concentrations were significantly lower than term ones (p<0.05). In the term pregnancies with labor, the highest median melatonin concentration was measured (p<0.05). A serum melatonin concentration≤34 pg/mL as a cut-off value determines late-term and postterm pregnancy with a sensitivity of 80.4% and a specificity of 81.4%. A serum melatonin concentration>29.35 pg/mL as a cut-off value determines presence of labor with a sensitivity of 82.1% and a specificity of 55.0%. In women with term pregnancies, with the measurement of serum melatonin, it is possible to predict the development of late-term and postterm pregnancies and whether these pregnancies undergo spontaneous labor. With further studies, these findings need to be supported before their routine clinical use.

Breastfeeding and complementary feeding in premature infants treated by a secondary reference service: a cohort study

Premature infants are vulnerable in the course of feeding practices, with lower rates of breastfeeding and inadequate feeding. To analyze breastfeeding rates, use of cow's milk and dietary inadequacies of premature infants in the second semester of Corrected Gestational Age (CGA), comparing them in two moments. This is a non-concurrent cohort with documentary analysis of medical records of 118 premature infants monitored at a secondary referral health service. Sociodemographic and perinatal data were analyzed in relation to the type of breastfeeding, feeding error and use of cow's milk in two moments: 6 months and 12 months of CGA. A reduction in breastfeeding rates was observed by the second semester of CGA (48.3% vs. 36.4%). The prevalence of dietary inadequacies was significant and showed no differences between the two periods (26.3 vs. 27.1%), but the rates of use of cow's milk increased in the second moment (11% vs. 26.3%). Birth weight less than 2000g was associated with a 4.2 times greater chance of artificial feeding in the first year of CGA. Low rates of breastfeeding, use of cow's milk and inadequate complementary feeding are expressive in premature infants whose families have low education and low income.

Association of Routinely Measured Proinflammatory Biomarkers With Abnormal MRI Findings in Asphyxiated Neonates Undergoing Therapeutic Hypothermia

Background: The neuroprotective treatment effect of therapeutic hypothermia (TH) following perinatal asphyxia may be negatively influenced by neonatal sepsis and concomitant inflammation. We aimed to correlate routinely used blood biomarkers for perinatal sepsis in cooled asphyxiated newborns with MRI findings.Methods: Perinatal data was retrospectively collected from 67 cooled asphyxiated newborns. Levels of C-reactive protein (CRP), white blood cells and platelets were analyzed before, during and after TH. Interleukin-6 blood levels were analyzed before initiation of TH. Magnetic resonance imaging (MRI) on postnatal day 5–7 was used defining short-term outcome. Adverse outcome was defined as death or adverse MRI findings. Amplitude-integrated electroencephalography (aEEG) was additionally analyzed and correlated with short-term MRI outcome.Results: Forty-nine newborns had favorable short-term MRI outcome. Perinatal data referring to perinatal sepsis did not differ significantly between groups. IL-6 levels before initiation of TH and CRP levels on day three and after TH were significantly higher in newborns with adverse short-term MRI outcome. Males with adverse short-term MRI outcome had significantly increased CRP values at the end of the cooling phase. aEEG strongly correlated with short-term MRI outcome.Conclusion: Routinely used blood biomarkers may be helpful early identifying newborns at high risk of unfavorable outcome and in need of close neurodevelopmental follow-up.

The data we have: Pregnancy and birth related data collection in Australia, Canada, Europe and the USA- A web-based survey of practice

ObjectiveTo determine the feasibility of combining routinely recorded perinatal data from several databases in high-income countries to assess the risk of recurrent stillbirth. MethodsWeb-based questionnaire survey with reminder emails and searching of relevant country websites. Results120 countries/regions in Canada, Europe and the USA were invited to participate and 83 (69%) responded. Of those one had no data, and two did not wish to take part. The remaining 80 were sent the questionnaire and 63 (53%) were completed. Twenty-seven countries/regions reported that they collect information on all perinatal events (including early pregnancy loss), 34 on live births and stillbirths and two only live births (stillbirths recorded in a separate database). Most countries (53/63) can link two or more pregnancies occurring in the same woman. Data and information extracted from the Australian and New Zealand Government websites showed that information on all perinatal events is collected nationally in New Zealand and in 5/8 regions in Australia. Both Australia and New Zealand can link two or more pregnancies occurring in the same woman. Maternal age and caffeine consumption were the most and least consistently collected demographic indicators respectively. Diabetes mellitus and mental health problems, birthweight and obstetric cholestasis the most and least consistently collected for medical conditions and pregnancy condition/complications. Procedures for gaining access to data vary between countries. ConclusionThis study demonstrates that it is possible to link pregnancies in the same woman to assess the risk of recurrent stillbirth using routinely collected perinatal data in all states/territories in Australia, 7/8 responding provinces/territories in Canada, 21/27 responding countries/regions in Europe, New Zealand and 26/28 responding states in the USA. The scope of the databases and quality and extent of data collected (thus their potential use) varied, as did procedures for accessing their data.