Neonatal hemorrhage stroke and severe coagulopathy in a late preterm infant after receiving umbilical cord milking:A case report

BACKGROUND Umbilical cord milking(UCM)is an alternative placental transfusion method for delayed umbilical cord clamping in routine obstetric practice,allowing prompt resuscitation of an infant.Thus,UCM has been adopted at some tertiary neonatal centers for preterm infants to enhance placental-to-fetal transfusion.It is not suggested for babies less than 28 wk of gestational age because it is associated with severe brain hemorrhage.For late preterm or term infants who do not require resuscitation,cord management is recommended to increase iron levels and prevent the development of iron deficiency anemia,which is associated with impaired motor development,behavioral problems,and cognitive delays.Concerns remain about whether UCM increases the incidence of intraventricular hemorrhage.However,there are very few reports of late preterm infants presenting with neonatal hemorrhage stroke(NHS)and severe coagulopathy after receiving UCM.Here,we report a case of a late preterm infant born at 34 wk of gestation.She abruptly deteriorated,exhibiting signs and symptoms of NHS and severe coagulopathy after receiving UCM on the first day of life.CASE SUMMARY A female preterm infant born at 34 wk of gestation received UCM after birth.She was small for her gestational age and described as vigorous with Apgar scores of 9 and 10 at one minute and five minutes of life,respectively.After hospitalization in the neonatal intensive care unit,she showed hypoglycemia and metabolic acidosis.The baby was administered glucose and sodium bicarbonate infusions.Intramuscular vitamin K1 was also used to prevent vitamin K deficiency.The baby developed umbilical cord bleeding and gastric bleeding on day 1 of life;a physical examination showed bilateral conjunctival hemorrhage,and a blood test showed thrombocytopenia,prolonged prothrombin time,prolonged activated partial thromboplastin time,low fibrinogen,raised D-dimer levels and anemia.A subsequent cranial ultrasound and computed tomography scan showed a left parenchymal brain hemorrhage with extension into the ventricular and subarachnoid spaces.The patient was diagnosed with NHS in addition to disseminated intravascular coagulation(DIC).Fresh frozen plasma(FFP)and prothrombin complex concentrate were given for coagulopathy.Red blood cell and platelet transfusions were provided for thrombocytopenia and anemia.A bolus of midazolam,intravenous calcium and phenobarbital sodium were administered to control seizures.The baby’s clinical condition improved on day 5 of life,and the baby was hospitalized for 46 d and recovered well without seizure recurrence.Our case report suggests that preterm infants who receive UCM should undergo careful clinical assessment for intracranial hemorrhage,NHS and severe coagulopathy that may develop under certain circumstances.Supportive management,such as intensive care,FFP and blood transfusion,is recommended when the development of massive NHS and associated DIC is suspected.CONCLUSION Our case report suggests that for late preterm infants who are small for gestational age and who receive UCM for alternative placental transfusion,neonatal health care professionals should be cautious in assessing the development of NHS and severe coagulopathy.Neonatal health care professionals should also be more cautious in assessing the complications of late preterm infants after they receive UCM.

Vγ9Vδ2-T lymphocytes have impaired antiviral function in small-for-gestational-age and preterm neonates

Preterm and small-for-gestational-age （SGA） neonates are vulnerable groups that are susceptible to various microbial infections. Vγ9Vδ2-T cells are critical components of the host immune system and have been demonstrated to play an important role in the defense against viral infection in adults. However, the characteristics of Vγ9Vδ2-T cells in children, especially the preterm and SGA populations, are poorly understood. Here, we examined the frequency and antiviral function of Vγ9Vδ2-T cells in neonates, including preterm, SGA and full-term babies. When compared to adults, neonates had a significantly lower percentage of Vγ9Vδ2-T cells in the blood. Upon influenza virus stimulation, neonatalVγ9Vδ2-T cells, especially from preterm and SGA babies, showed markedly decreased and delayed antiviral cytokine responses than those of adults. In addition, the antiviral responses of neonatal Vγ9Vδ2-T cells were positively correlated with gestational age and birth weight. Finally, a weaker expansion ofVγ9Vδ2-T cells by isopentenyl pyrophosphate （IPP） was shown in neonates than the expansion in adults. Our data suggest that the depressed antiviral activity and decreased frequency of Vγ9Vδ2-T cells may likely account for the high susceptibility to microbial infection in neonates, particularly in preterm and SGA babies. Improving Vγ9Vδ2-T -cell function of neonates may provide a new way to defend against virus infection.

Perinatal outcomes of frozen-thawed embryo transfer following blastocyst-stage embryo transfer compared to those of cleavage-stage embryo transfer:analysis of 9408 singleton newborns using propensity score analysis

Objective:Regarding frozen-thawed embryo transfer(FET),there is limited consensus on whether extending embryo culture from the cleavage stage to the blastocyst stage affects perinatal outcomes.This study aimed to compare perinatal outcomes of singletons between blastocyst-stage embryo transfer(BT)and cleavage-stage embryo transfer(CT)in FET.Methods:A total of 9408 FET cycles that met the inclusion criteria were included in this retrospective cohort study between 2019 and 2022.Blastocyst-stage embryo transfers were performed in the BT group,and cleavage-stage embryo transfers were performed in the CT group.Multivariate logistic regression analyses were performed,as well as propensity score matching(PSM)to adjust for confounders.Results:After PSM,a higher risk of pre-term birth(PTB;odds ratio[OR]:1.23,95%confidence interval[CI]:1.00-1.50,P=0.048)and being large for gestational age(LGA;OR:1.16,95%CI:1.00-1.35,P=0.050)was observed in the BT group compared to that in the CT group.After stratified PSM,in the subgroup under 35 years of age,only an increased risk of LGA was observed in the BT group compared to the CT group.Perinatal outcomes in the double-embryo transfer subgroup were similar to those in the unstratified group.However,in the subgroup beyond 35 years of age and the single embryo transfer subgroup,perinatal outcomes were not statistically different between the BT and CT groups(P>0.05).Conclusions:In FET,prolonged embryo culture to the blastocyst stage increased the risk of PTB and LGA in single fetuses.However,stratified analysis based on age and the number of transferred embryos yielded different results,necessitating further mechanistic studies.

Men becoming fathers by injection were more often age intracytoplasmic sperm born small for gestational

Being born with nonoptimal birth characteristics decreases the chance of becoming a father. Urogenital malformations as well as metabolic syndrome are more common in men born small for gestational age （SGA） and could be contributing factors to the reduced fertility rate seen in these men. It could imply that men becoming fathers by assisted reproductive technology （ART） more often are born with low birth weight （LBW）, preterm, and/or SGA than men conceiving without treatment and also that men where intracytoplasmic sperm injection （ICSI） had to be performed more often are born with nonoptimal birth characteristics than men where conventional in vitro fertilization （IVF） successfully could be used. In this retrospective, case-control study using Swedish national registers, we compared the birth characteristics of 1206 men who have become fathers by ART with a control group consisting of age-matched men who became fathers without treatment. The differences in birth characteristics between men becoming fathers by IVF and ICSI were also assessed. For men becoming fathers by ART, OR of being born with LBW was 1.66 （95% CI = 1.17-2.36） compared with fathers who conceived without treatment. OR of being born prematurely was 1.32 （95% CI = 1.00-1.77）. Men becoming fathers via ICSI had a doubled increased likelihood of being born SGA compared with men who became fathers via IVF （OR = 2.12; 95% CI = 1.17-3.83）. In conclusion, we have found that men becoming fathers by ICSI treatments had more often been born SGA than men becoming fathers by conventional IVF.

Influential and prognostic factors of small for gestational age infants

Background Small for gestational age （SGA） infants are associated with a high rate of oligohydramnios, stillbirth and cesarean delivery. Among SGA patients there is a higher risk of neonatal complications, such as polycythemia, hyperbilirubinemia, and hypothermia. Additionally, the SGA infant is prone to suffer from major neurologic sequelae, as well as cardiovascular system disease, in later life. Proper monitoring and therapy during pregnancy are, therefore, of utmost importance. The present study aimed to investigate the influential and prognostic factors of SGA infants.Methods From January 2001 to June 2007, a total of 55 SGA neonatal infants were included in a study group. All were born at Peking Union Medical College Hospital, with regular formal antenatal examinations. In addition, a total of 122 cases of appropriate for gestational age （AGA） infants were born at the same time and were registered into a control group. All cases were singleton pregnancies with detailed information of the maternal age, gravidity, parity, maternal height and weight, complications, uterine height and abdominal circumference, results from transabdominal ultrasonography between 32-38 gestational weeks, pregnancy duration, delivery manner, placenta, umbilical cord, and neonatal complications.Results Significant differences were observed in placenta weight and neonatal malformations between the study and control groups. Multivariate analysis revealed increased parity, maternal hyperthyroidism and hyperthyroidism history as risk factors. Fetal abdominal circumferences less than 30 and 32 cm at 32-38 gestational weeks respectively, as determined by ultrasonography, resulted in a Youden index of 0.62. Conclusions SGA infants were associated with a greater risk of smaller placentas and infant malformations. Increased parity, maternal hyperthyroidism, and a hyperthyroid history were risk factors for SGA infants. Fetal abdominal circumference less than 30 cm at 32 gestational weeks and less than 32 cm at 38 weeks, as determined by ultrasonograohy, was considered an effective index for SGA.

Peak systolic velocity Doppler of middle cerebral artery in small for gestational age （SGA） fetus

BACKGROUND： Small for gestational age （SGA） has high frequency which increases the risk of long-term adverse outcomes. Thus the aim of this study was to evaluate peak systolic velocity Doppler of middle cerebral artery （MCA） in SGA fetus in order to find appropriate method to diagnosis SGA sooner. MATERIALS and METHODS： This prospective longitudinal study was conducted on 90 pregnant women with a diagnosis of SGA fetus and 90 pregnant women with normal fetus. Then MCA and umbilical artery assessment were performed for all subjects and compared between two groups. RESULTS： Doppler assessment showed that umbilical artery PI was significantly higher in SGA group as compared to normal group （1.114-0.37 vs 0.984-0.18, P = 0.003）, while MCA PI was significantly lower in SGA group （1.77±0.44 vs 1.92±0.47, P = 0.028）. On the other hand, PSV did not differ between the groups （P = 0.592）. Moreover, we found that PSV was more in SGA group by grouping maternal age （〈 27 years） （P = 0.006）, and gestational age （〉 34 weeks） （P 〈 0.001）. CONCLUSION： The results of this study suggest that MCA PI decreased significantly in SGA fetuses, while UA PI increased in this group. Moreover, PSV increased in this group when evaluated in different subgroups （based on maternal age and gestational age）.

Prior Preterm Birth and Birthweight Below the 5 th Percentile are Independent Risk Factors for Recurrence of a Small for Gestational Age Neonate

Objective::This study aimed to determine:(1)whether recurrent deliveries of a small for gestational age(SGA)neonate are associated with increased obstetrical or neonatal complications;(2)whether the risk factors that can predict small for gestational age(SGA)recurrence.Methods::This study was based on Soroka Medical Center's Obstetrics electronic database.The database consisted of 109022 women who had 320932 deliveries between the year 1988-2014.The study cohort included 6.8%(7368/109022)of these patients who gave birth to a singleton SGA neonate on their first delivery and had more than one delivery.The study population was divided into two groups according to the outcome of the subsequent delivery:(1)women with sporadic SGA who delivered a non-SGA neonate(n=5416);(2)women with recurrent SGA(n=1952).SGA defined as birthweight<10 th percentile.Maternal and neonatal complications were compared between the two groups.Logistic regression was used to determine independent risk factors for SGA recurrence.Results::The prevalence of birthweight<5 th percentile was higher among the recurrent SGA group in the first delivery(P<0.001).Bedouin ethnicity was more prevalent in the recurrent SGA group(P<0.001).The rate of preterm delivery was higher in the first delivery of the recurrent SGA group(P=0.015).The sporadic SGA group had a higher rate of perinatal mortality during the first pregnancy(P=0.017).The rate of severe hypertension(P=0.005),polyhydramnios,meconium-stained amniotic fluid,nonreassuring fetal heart rate and total perinatal mortality(P<0.001)were higher in the second delivery of the recurrent SGA group.In a logistic regression model,preterm delivery and birthweight<5 th percentile at the first delivery was found to be independent risk factors for recurrence of an SGA neonate in the subsequent birth(relative risks:1.530,confidence interval:1.249-1.875;relative risks:1.826,confidence interval:1.641-2.030,respectively).Conclusion::Women with recurrent SGA neonates have specific clinical characteristics.Among women who deliver an SGA neonate,preterm delivery,and birthweight<5 th percentile are independent predictors for its recurrence.

Impact of inflammatory bowel disease activity and thiopurine therapy on birth weight: A meta-analysis

AIM To investigate the effect of disease activity or thiopurine use on low birth weight and small for gestational age in women with inflammatory bowel disease(IBD).METHODS Selection criteria included all relevant articles on the effect of disease activity or thiopurine use on the risk of low birth weight(LBW) or small for gestational age(SGA) among pregnant women with IBD. Sixtynine abstracts were identified,35 papers were full text reviewed and,only 14 of them met inclusion criteria. Raw data were extracted to generate the relative risk of LBW or SGA. Quality was assessed using the Newcastle Ottawa Scale.RESULTS This meta-analysis is reported according to PRISMA guidelines. Fourteen studies met inclusion criteria,and nine reported raw data suitable for meta-analysis. We found an increased risk ratio of both SGA and LBW in women with active IBD,when compared with women in remission: 1.3 for SGA(4 studies,95%CI: 1.0-1.6,P = 0.04) and 2.0 for LBW(4 studies,95%CI: 1.5-2.7,P < 0.0001). Women on thiopurines during pregnancy had a higher risk of LBW(RR 1.4,95%CI: 1.1-1.9,P = 0.007) compared with non-treated women,but when adjusted for disease activity there was no significant effect on LBW(RR 1.2,95%CI: 0.6-2.2,P = 0.6). No differences were observed regarding SGA(2 studies; RR 0.9,95%CI: 0.7-1.2,P = 0.5). CONCLUSION Women with active IBD during pregnancy have a higher risk of LBW and SGA in their neonates. This should be considered in treatment decisions during pregnancy.

A Case-Control Study on Leisure Time Physical Activity (LTPA) during the Last Three Months of Pregnancy and Foetal Outcomes in Italy

The association between Leisure Time Physical Activity (LTPA) during pregnancy and foetal outcomes has been extensively investigated. However, epidemiological studies specifically referred to LPTA in the last months of pregnancy are scarce. We evaluated the association between LPTA and the risk of both preterm delivery and small for gestational age (SGA) during the last three months of pregnancy in Italy. A nationwide case-control study was performed in nine Italian cities. A total of 299 preterm delivery, 364 SGA and 855 controls were enrolled in the study. A self-administered questionnaire was used to assess socio-demographic variables, medical and reproductive history, life-style habits and LTPA referred to the last three months of pregnancy. Univariate and multivariate regression analyses were performed in order to estimate Odds ratios and 95% CI. LTPA during the last three months of pregnancy decreases the risk of preterm delivery (adjusted OR = 0.56;95% CI 0.39 - 0.79). Among the different types of physical activity, walking, the most frequently referred activity, appears significantly protective against preterm delivery (adjusted OR = 0.53;95% CI 0.36 - 0.81). Moreover, a small protective effect of walking was evidenced against SGA (adjusted OR = 0.72;95% CI 0.51 - 1.00). In conclusion, a mild physical activity such as walking in the last three months of pregnancy seems to reduce the risk of preterm delivery and, at a lesser extent, of SGA, confirming the beneficial effects of physical activity along the whole pregnancy.

Meta-Analysis on the associations between Prenatal Perfluoroalkyl Substances Exposure and Adverse Birth Outcomes

The epidemiological associations between the prenatal perfluoroalkyl substances(PFASs)exposure and the reproductive outcomes remain controversial.A continuous evaluation is needed to combine the inconsistent results.In this study,we explored the associations between PFASs exposure and the low birth weight(LBW),preterm birth and small for gestational age(SGA).The quality of selected literature,quantitative estimates,publication bias and subgroup analysis were performed on the basis of 17 retrieved articles published before December 2020.The results showed a significant positive association between the perfluorooctane sulfonate(PFOS)exposure and the risk of LBW[Odds ratio(OR)=1.17;95%confidence interval(CI):1.01,1.36;heterogeneity:P=0.30,I2=17%].The positive association was also observed between the PFOS and the risk of preterm birth(OR=1.19;95%CI:1.01,1.39,P=0.007;I2=62%).There was a paucity of evidence regarding the negative effects of perfluorooctanoic acid(PFOA),perfluorohexanesulfonic acid(PFHxS)and perfluorononanoic acid(PFNA)on the pregnancy outcomes.The findings from the subgroup analysis(the sampling period,the birth gender and biologic specimens)did not substantially altered the results of the overall pooled estimate ORs.The increased prevalence of negative birth outcomes with gestational PFASs exposure warrants further explorations from biological process perspective.

Multiple Sclerosis in Pregnancy—A Practical Guide for the Obstetrician

Technological advances, a deeper understanding of disease processes and increased sophistication of therapeutic methods have all led to better outcomes in rare diseases which previously had devastating effects on many women’s lives. The inevitable result of this progress is that women, who in the past did not contemplate pregnancy because of significant morbidity, now get to adulthood and are reasonably “disease free” enough to have their own families. The ever expanding, but relatively new specialty of Obstetric medicine seeks to further improve the outcome in pregnant women with intercurrent disease by enhancing the literature base, thereby contributing to the creation of appropriate guidance in the management of these patients. This article is a brief but useful guide for the busy obstetrician who may have limited experience in dealing with multiple sclerosis in pregnant women.

Association between gestational anemia in different trimesters and neonatal outcomes:a retrospective longitudinal cohort study

Background Previous studies investigated the association between gestational anemia and neonatal outcomes.However,few studies explored whether the effects of gestational anemia could be eliminated by subsequent correction of anemia in the later stages of pregnancy.This study aimed to investigate the relationship between anemia in different trimesters and neonatal outcomes.Methods The study was conducted in Shanghai,China,with a sample of 46,578 pregnant women who delivered between January 1,2016 and July 1,2019.A multivariable logistic regression model was adopted to analyse the associations between maternal anemia and neonatal outcomes.Results The incidence of gestational anemia was 30.2%,including 4.4%in the first trimester,9.6%in the second trimester,and 16.2%in the third trimester.Only 24.5%(507/2066)of anemia that occurred in the first trimester and 29.6%(1320/4457)that occurred in the second trimester could be corrected in the later stages of pregnancy.Anemia occurring in the first trimester was associated with small for gestational age[odds ratio(OR)1.46;95%confidence interval(CI)1.20-1.78]and with fetal distress(OR 1.23;95%CI 1.08-1.40).Anemia corrected in the first trimester also was associated with a higher risk of small for gestational age.Conclusions Gestational anemia is a public health problem in China impacting neonatal health.Anemia in pregnancy could be corrected in only about a quarter of the women.Anemia in the first trimester,whether corrected or not,still led to lower birth weight;therefore,the prevention of anemia prior to pregnancy is important.