Preterm Singleton Birth Rate during the COVID-19 Lockdown: A Population-Based Study

Objective The aim of the study is to evaluate the effect of the coronavirus disease 2019 (COVID-19) pandemic national lockdown period on the rate of singleton preterm births in Israel. Study Design This is a population-based cohort study of 3,41,291 singleton infants born in the months of January to July 2017 to 2020. Multivariable logistic regression analyses were used to estimate the influence of period and year on the rates of preterm births during the lockdown period (11th March − 5th May 2020) compared with rates before (January 1st 2020 − March 10th 2020), and after the lockdown (May 6th 2020–June 30th 2020) and to the corresponding periods in 2017to 2019. Results During the lockdown period the preterm birth rate (primary outcome) decreased by 9.7% from 5.05 to 4.56% in the pre-lockdown period (p = 0.006), an adjusted decrease of −0.52% (95% confidence interval −0.89%; −0.15%), odds ratio 0.898 (95% confidence interval 0.832; 0.970). Conclusion The rate of singleton preterm births declined by 9.7% during the COVID-19 pandemic national lockdown period in Israel. Key Points

Neonates with mild hypoxic–ischaemic encephalopathy receiving supportive care versus therapeutic hypothermia in California

ObjectiveThe use of therapeutic hypothermia (TH) for mild hypoxic–ischaemic encephalopathy (HIE) remains controversial and inconsistent. We analysed trends in TH and maternal and infant characteristics associated with short-term outcomes of infants with mild HIE.DesignRetrospective cohort analysis of the California Perinatal Quality Care Collaborative database 2010–2018. E-value analysis was conducted to determine the potential impact of unmeasured confounding.SettingCalifornia neonatal intensive care units.Patients1364 neonates with mild HIE.InterventionsSupportive care versus TH.Main outcome measuresFactors associated with TH and mortality.ResultsThe proportion of infants receiving TH increased from 46% in 2010 to 79% in 2018. TH was more likely in the setting of singleton birth (OR 2.69, 95% CI 1.21 to 5.39), no major birth defects (OR 2.18, 95% CI 1.42 to 3.30), operative vaginal delivery (OR 3.04, 95% CI 1.80 to 5.10) and 5-minute Apgar score ≤5 (OR 3.17, 95% CI 2.43 to 4.13). Mortality was associated with small for gestational age (OR 5.79, 95% CI 1.90 to 18.48), <38 weeks’ gestation (OR 7.31 95% CI 2.39 to 24.93), major birth defects (OR 11.62, 95% CI 3.97 to 38.00), inhaled nitric oxide (OR 12.73, 95% CI 4.00 to 44.53) and nosocomial infection (OR 7.98, 95% CI 1.15 to 47.03). E-value analyses suggest that unmeasured confounding may have contributed to some of the observed effects.ConclusionsVariation in management of mild HIE persists, but therapeutic drift has become more prevalent over time. Further studies are needed to assess long-term outcomes alongside resource utilisation to inform evidence-based practice.

Incident Heart Failure Within the First and Fifth Year after Delivery Among Women With Hypertensive Disorders of Pregnancy and Prepregnancy Hypertension in a Diverse Population

Background Hypertensive disorders of pregnancy (HDP) and pre‐pregnancy hypertension are associated with increased morbidity and mortality for the mother. Our aim was to investigate the relationships between HDP and pre‐pregnancy hypertension with maternal heart failure (HF) within 1 and 5 years of delivery and to examine racial/ethnic differences. Methods and Results We conducted a retrospective cohort study in South Carolina (2004–2016) involving 425 649 women aged 12 to 49 years (58.9% non‐Hispanic White [NHW], 31.5% non‐Hispanic Black [NHB], 9.6% Hispanic) with a live, singleton birth. Incident HF was defined by hospital/emergency department visit and death certificate data. Pre‐pregnancy hypertension and HDP (preeclampsia, eclampsia, or gestational hypertension) were based on hospitalization/emergency department visit and birth certificate data (i.e., gestational hypertension for HDP). The 425 649 women had pre‐pregnancy hypertension without superimposed HDP (pre‐pregnancy hypertension alone; 0.4%), HDP alone (15.7%), pre‐pregnancy hypertension with superimposed HDP (both conditions; 2.2%), or neither condition in any pregnancy (81.7%). Incident HF event rates per 1000 person‐years were higher in NHB than NHW women with HDP (HDP: 2.28 versus 0.96; both conditions: 4.30 versus 1.22, respectively). After adjustment, compared with women with neither condition, incident HF risk within 5 years of delivery was increased for women with pre‐pregnancy hypertension (HR,2.55, 95% CI: 1.31–4.95), HDP (HR,4.20, 95% CI: 3.66–4.81), and both conditions (HR,5.25, 95% CI: 4.24–6.50). Conclusions Women with HDP and pre‐pregnancy hypertension were at higher HF risk (highest for superimposed preeclampsia) within 5 years of delivery. NHB women with HDP had higher HF risk than NHW women, regardless of pre‐pregnancy hypertension.

Association of maternal total cholesterol with SGA or LGA birth at term: The Japan Environment and Children's Study

Context Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in mid-pregnancy are associated with small- (SGA) or large- (LGA) for-gestational-age independent of pre-pregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. Objective To prospectively investigate the association between maternal TC in mid-pregnancy and SGA or LGA. Design and Setting The Japan Environment and Children’s Study is a nationwide prospective birth cohort study in Japan. Participants A total of 37,449 non-diabetic, non-hypertensive mothers with singleton birth at term without congenital abnormalities. Outcome Measures Birth weight for the gestational age &lt;10 percentile and ≥90 percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. Results The mean gestational age at blood sampling was 22.7±4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, pre-pregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and Study Areas, one standard deviation decrement of maternal TC was linearly associated with SGA [odds ratio (OR): 95% confidence intervals (CI) = 1.20: 1.15-1.25]. In contrast, one standard deviation increment of maternal TC was linearly associated with LGA [OR: 95% CI = 1.13: 1.09-1.16]. Associations did not differ according to pre-pregnancy BMI and gestational weight gain (p for interaction&gt;0.20). Conclusion Maternal TC levels in mid-pregnancy were associated with SGA or LGA in Japanese. Maternal TC in mid-pregnancy may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

P-746 Obstetric outcomes of singleton birth after hysteroscopic division of septate uterus

Study question The aim of this study is to determine the obstetric outcomes in patients with a singleton birth after hysteroscopic division of septate uterus. Summary answer The data suggest excellent obstetric outcomes for singleton gestation after hysteroscopic division of a septate uterus reaching either the internal or the external cervical os. What is known already Septate uterus is a rare Müllerian anomaly with major impact on reproductive outcomes, particularly with a septum over 10mm. Controversy still exists over the need for surgical correction of the septum due to conflicting data on outcomes, particularly in women with histories of good obstetric outcomes and incidental septum findings. Placental location in relation to the septum may account for such conflicting reports. Most data on reproductive outcomes after hysteroscopic surgical correction combine both septate and subseptate uteri. There is limited published data on obstetric outcomes after hysteroscopic surgical correction of septate uteri, especially septate uteri reaching the external os. Study design, size, duration This retrospective cohort study included 107 patients with infertility and/or recurrent pregnancy loss (RPL) who received treatment between 2002 -2019. The study group included 24 patients with a singleton birth after hysteroscopic correction of septate uterus (Class Va; ASRM classification) that was diagnosed on trans-vaginal 3D ultrasound. The control group included 83 patients with a singleton birth who had normal endometrial cavity on hysteroscopy during the same period of time, before starting treatment. Participants/materials, setting, methods This study was conducted at an infertility clinic affiliated with a teaching hospital. In the study group the septum reached the internal or the external cervical os in 14 and 10 patients respectively. After hysteroscopic correction, all patients were offered various infertility treatments depending on the underlying etiology. The inclusion criterion in this study was to have a singleton birth after hysteroscopy. Demographic and clinical data and obstetric outcomes were compared between the two groups. Main results and the role of chance There was no significant difference in mean age, infertility duration, infertility type and incidence of male infertility or ovulatory disorders between the two groups. There was a significantly higher BMI (0.048), and a higher incidence of history of miscarriage (P=0.002) and history of RPL (P=0.017) in the study group. There was significant lower incidence of tubal factors infertility (P=0.005) and endometriosis (P=0.03) in the study group, therefore there was higher incidence of spontaneous conception (70.8% vs 19.3%; P=0.000) and lower incidence of conception with IVF-ET (20.8% vs 66.3%; P=0.000) in the study group compared to the control group respectively. There was significantly higher incidence of prophylactic cervical cerclage (17.4% vs 0%; P=0.000), and delivery by CS (69.6% vs 41.2%; P=0.019) and lower incidence of vaginal delivery (30.4% vs 58.8%; P=0.019), in the study group compared to the control group. There was no significant difference in gestational age in weeks (38.3 + 1.8 vs 38.6 + 2.0), newborn birth weight in grams (3173.9 + 630.0 vs 3202.1 + 555.6), incidence of premature birth (12.5% vs 12.2%), or other obstetric complications (25% vs 17.6%) between the study and the control groups respectively. For premature births, mean gestational age was 34.3 + 0.47 and 34.6 + 1.2 weeks in the study and control groups respectively. Limitations, reasons for caution A retrospective study has its own inherent bias. Furthermore, the small sample size is explained by the fact that a septate uterus is a rare anomaly leading to difficulties finding cases and organizing a prospective study to achieve a larger sample size. A multicenter prospective study is needed. Wider implications of the findings Regardless of whether the septum reached the internal or external os, there were excellent obstetric outcomes in singleton gestations after hysteroscopic correction of septate uteri. There was no increased risk with septate uteri involving the cervix. Hysteroscopic surgical correction should be the treatment of choice for patients with septate uteri. Trial registration number Not Applicable

P–746 Obstetric outcomes of singleton birth after hysteroscopic division of septate uterus

Study question The aim of this study is to determine the obstetric outcomes in patients with a singleton birth after hysteroscopic division of septate uterus. Summary answer The data suggest excellent obstetric outcomes for singleton gestation after hysteroscopic division of a septate uterus reaching either the internal or the external cervical os. What is known already Septate uterus is a rare Müllerian anomaly with major impact on reproductive outcomes, particularly with a septum over 10mm. Controversy still exists over the need for surgical correction of the septum due to conflicting data on outcomes, particularly in women with histories of good obstetric outcomes and incidental septum findings. Placental location in relation to the septum may account for such conflicting reports. Most data on reproductive outcomes after hysteroscopic surgical correction combine both septate and subseptate uteri. There is limited published data on obstetric outcomes after hysteroscopic surgical correction of septate uteri, especially septate uteri reaching the external os. Study design, size, duration This retrospective cohort study included 107 patients with infertility and/or recurrent pregnancy loss (RPL) who received treatment between 2002 –2019. The study group included 24 patients with a singleton birth after hysteroscopic correction of septate uterus (Class Va; ASRM classification) that was diagnosed on trans-vaginal 3D ultrasound. The control group included 83 patients with a singleton birth who had normal endometrial cavity on hysteroscopy during the same period of time, before starting treatment. Participants/materials, setting, methods This study was conducted at an infertility clinic affiliated with a teaching hospital. In the study group the septum reached the internal or the external cervical os in 14 and 10 patients respectively. After hysteroscopic correction, all patients were offered various infertility treatments depending on the underlying etiology. The inclusion criterion in this study was to have a singleton birth after hysteroscopy. Demographic and clinical data and obstetric outcomes were compared between the two groups. Main results and the role of chance There was no significant difference in mean age, infertility duration, infertility type and incidence of male infertility or ovulatory disorders between the two groups. There was a significantly higher BMI (0.048), and a higher incidence of history of miscarriage (P = 0.002) and history of RPL (P = 0.017) in the study group. There was significant lower incidence of tubal factors infertility (P = 0.005) and endometriosis (P = 0.03) in the study group, therefore there was higher incidence of spontaneous conception (70.8% vs 19.3%; P = 0.000) and lower incidence of conception with IVF-ET (20.8% vs 66.3%; P = 0.000) in the study group compared to the control group respectively. There was significantly higher incidence of prophylactic cervical cerclage (17.4% vs 0%; P = 0.000), and delivery by CS (69.6% vs 41.2%; P = 0.019) and lower incidence of vaginal delivery (30.4% vs 58.8%; P = 0.019), in the study group compared to the control group. There was no significant difference in gestational age in weeks (38.3 + 1.8 vs 38.6 + 2.0), newborn birth weight in grams (3173.9 + 630.0 vs 3202.1 + 555.6), incidence of premature birth (12.5% vs 12.2%), or other obstetric complications (25% vs 17.6%) between the study and the control groups respectively. For premature births, mean gestational age was 34.3 + 0.47 and 34.6 + 1.2 weeks in the study and control groups respectively. Limitations, reasons for caution A retrospective study has its own inherent bias. Furthermore, the small sample size is explained by the fact that a septate uterus is a rare anomaly leading to difficulties finding cases and organizing a prospective study to achieve a larger sample size. A multicenter prospective study is needed. Wider implications of the findings: Regardless of whether the septum reached the internal or external os, there were excellent obstetric outcomes in singleton gestations after hysteroscopic correction of septate uteri. There was no increased risk with septate uteri involving the cervix. Hysteroscopic surgical correction should be the treatment of choice for patients with septate uteri. Trial registration number Not applicable

Should singleton birth weight standards be applied to identify small-for-gestational age twins?: analysis of a retrospective cohort study

Background Twin birth weight percentiles are less popular in clinical management among twin pregnancies compared with singleton ones in China. This study aimed to compare the incidence and neonatal outcomes of small for gestational age (SGA) twins between the use of singleton and twin birth weight percentiles. Methods This was a retrospective cohort study of 3,027 pregnancies with liveborn twin pairs at gestational age of > 28 weeks. The newborns were categorized as SGA when a birthweight was less than the 10th percentile based on the singleton and twin references derived from Chinese population. Logistic regression models with generalized estimated equation (GEE) were utilized to evaluate the association between SGA twins and neonatal outcomes including neonatal unit admission, neonatal jaundice, neonatal respiratory distress (NRDS), neonatal asphyxia, ventilator support, hypoxic ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intracranial hemorrhage (ICH), culture-proven sepsis, neonatal death within 28 days after birth as well as the composite outcome. Results The incidence of SGA was 33.1 % based on the singleton reference and 7.3 % based on the twin reference. Both of SGA newborns defined by the singleton and twin references were associated with increases in neonatal unit admission, neonatal jaundice and ventilator support. In addition, SGA newborns defined by the twin reference were associated with increased rates of BPD (aOR, 2.61; 95 % CI: 1.18–5.78) as well as the severe composite outcome (aOR, 1.93; 95 % CI: 1.07–3.47). Conclusions The use of singleton birth weight percentiles may result in misdiagnosed SGA newborns in twin gestations and the twin birth weight percentiles would be more useful to identify those who are at risk of adverse outcomes.

The risk of major structural birth defects associated with seasonal influenza vaccination during pregnancy: a population-based cohort study

Objective: Seasonal inactivated influenza vaccine (IIV) is recommended during pregnancy to protect both mothers and infants from severe infection. Most studies have evaluated the risk of major structural birth defects in infants associated with prenatal administration of pandemic IIV. Our aim was to estimate the risk in infants associated with prenatal administration of seasonal IIV. Design: Retrospective population-based observational study Setting: Western Australia Population or sample: All pregnant women with a singleton birth from 2012-2016 Methods: 125,866 singleton births were linked to the state’s registers for congenital anomalies and a state prenatal vaccination database. We estimated prevalence ratios (PR) of any major structural birth defect and defects by organ system. Inverse probability treatment weighting factored for baseline probability for vaccination. Bonferroni correction was applied to account for multiple comparisons. Main outcome measures: Prevalence ratios by vaccination and major structural birth defects categories or specific birth defects diagnosed within one month of birth or within six years of life. Results: 3.9% of births had a major structural birth defect. IIV exposure during the first trimester was not associated with diagnosis of any major structural birth defect diagnosed within one month of birth (PR 0.98, 95% CI: 0.77, 1.28) or within six years of life (PR 1.02, 95% CI: 0.78, 1.35). We identified no increased risk in specific birth defects associated with IIV. Conclusions: Results suggest there is no association between maternal influenza vaccination and risk of major structural birth defects. These results support the safety of IIV administration during pregnancy.

Insulin-like growth factor-1 and growth in infants 0-6 months of age

Background During infancy, growth is affected by many factors, including hormones. Insulin-like growth factor-1 (IGF-1) is a hormone with an important role in regulating somatic growth and organ development. Objective To analyze for possible correlations between IGF-1 levels and infant growth from 0-6 months of age. Methods A prospective study was conducted on 38 infants from birth to 6 months of age. Inclusion criteria were full-term newborns with normal birth weight and singleton birth. Serum IGF-1 was measured twice, from umbilical cord blood at birth and at 6 months of age. Anthropometric measurements were made every three months. Paired T-test was used to analyze mean IGF-1 among time points, and Pearson’s correlation test was used to analyze IGF-1 levels and growth. Results Mean IGF-1 level decreased from birth to 6 months of age (89.6 ng/mL vs. 48.3 ng/mL, respectively; P<0.001). Delta IGF-1 had positive significant correlations with delta weight at 3 months (r=0.347; P=0.033) and 6 months (r=0.386; P=0.017), as well as delta head circumference at 3 months (r= 0.356; P=0.028) and 6 months (r=0.357; P=0.028). However, there were significant negative correlations between umbilical cord IGF-1 with delta body weight (r= −0.459; P=0.004) and delta length at 6 months (r= −0.414; P=0.010). Conclusions. There iss a decrease in IGF-1 levels at the first 6 months of life. Umbilical cord IGF-1 level has negative correlations with the weight and length increment at the age of 6 months.