Neonatal & Perinatal

P
Toti, C De Felice, MLD Plameri, et al (Univ of Siena, Italy; Univ of Antwerp, Wilrijk, Belgium)


Inflammatory Pathogenesis of Cortical Polymicrogyria: An Autopsy Study.



Pediatr Res 44: 291-296, 1998.

   


This is a study of 32 fetuses spontaneously aborted between 15 and 26 weeks’ gestation because of excessive ascending amnionitis.

    


Abnormalities in cortical morphology of the brain, can be caused by infection in the fetal adnexa (funisitis – polymorphonuclear leukocytes within the wall of umbilical cord vessels), and the subsequent generation of free radicals.

    


During hypoxia, the brain generates free radicals. This hypoxia along with free radical generation can cause nonspecific indirect cortical injury that could lead to polymicrogyria in fetuses who survive.

   

OD
Saugstad, T Rootwelt, (Natl Hosp, Oslo, Norway; Univ of Oslo, Norway)


Resuscitation of Asphyxiated Newborn Infants with Room Air or Oxygen: An International Controlled Trial: The Resair 2 Study.


Pediatrics 102:e1, 1998.

  


Most newborn infants with asphyxia are resuscitated with 100% oxygen, although such high oxygen concentrations could generate oxygen radicals that could cause cerebral injury. Therefore, resuscitation with a lower concentration of oxygen (room air) was studied as a way to treat newborns with asphyxia.

  


Methods: Ten international centers, most of which were located in developing countries, enrolled 609 newborn infants with asphyxia who weighed 1000g or more into this study. Patients were allocated to receive resuscitation with either 100% oxygen (321 babies) or with room air (288 babies), and median gestational age 38 weeks. American Heart Association techniques for resuscitation were used as guidelines, with a ventilation target frequency of 40 to 60 breaths/min. The number of deaths during the first week of life was compared between the groups, as was the presence hypoxic-ischemic encephalopathy. The groups were also compared on the basis of Apgar scores, heart rate at 90 seconds, time to first breath, time to first cry and arterial blood gas and acid base status.

   


All other parameters were almost the same in both the groups. However, arterial partial pressure of oxygen was significantly higher in the 100% oxygen group at 30 minutes after resuscitation. The room air group had significantly better Apgar score at 1 minute. Resuscitation was considered ineffective if the infants developed bradycardia, central cyanosis or both after 90 seconds; failure rates in the 100% oxygen and room air groups were similar.

  


Conclusion: The resuscitation of newborn infants with asphyxia with room air is at least as successful as resuscitation with 100% oxygen. In fact, the infants receiving room air had significantly better 1-minute Apgar score, a shorter time to first cry and a shorter time to first breath. The latter difference may be explained by a possible effect of 100% oxygen in depressing ventilation. The data presented in this article may have important implications for centres in both developing and developed countries.

   


Editorial comment : Each year a million babies die and that an equal number suffer permanent neurologic damage as a result of birth asphyxia. In developing countries, most deliveries probably occur in the home in the presence of a traditional health care worker who may be able to deliver mouth-to-mouth resuscitation if tactile stimulation and drying the infant fail to elicit respiratory efforts. Where electrical suctioning is not available, manual suctioning e.g. with bulb syringes, and bag and mask ventilation (with self-inflating bags) available to health care workers. The study had significant limitations and was too small to prove much. One has to enroll 7000 infants to demonstrate a significant reduction in brain injury or a change in the mortality rate from 24% to 21% . Such a study is unlikely to see the light of day.

   

DM
Casalaz, N Marlow, BD Speidel (Univ of Bristol, England; Southmead Hosp, Bristol, England)


Outcome of Resuscitation Following Unexpected Apparent Stillbirth


Arch Dis Child Fetal Neonatal Ed 78:F112-F115, 1998.

  


Few data are available regarding the outcome of infants born with no audible heartbeat at 1 minute and this was reviewed to evaluate the prevalence of intact survival in these infants and to identify predictors that might be of value to the clinical team.

  


The outcome of 42 successfully resuscitated stillborn children was reviewed with the conclusion that of the unexpected apparent stillbirths successfully resuscitated, 52% died or survived severely disabled. About 10% had an equivocal outcome and 36% survived apparently intact. In these circumstances, vigorous resuscitation is clearly indicated.

  


Editor comments : Unexpected Apparent Stillbirths in the United States was last reviewed in the 1992 -Year Book of Neonatal-Perinatal Medicine and it was found that significant handicap was detected in the 70% of the survivors. Poor outcome was associated with late return of the heartbeat, delayed respiration, neonatal acidemia, and the early onset of seizures.

  


Dr. Ingle’s comments: As far as India is concerned, we have very limited resources. I feel unless the child is very precious born after say treatment for infertility or in a very elderly patients, such efforts should not be done for a simple reason that only 36% of babies will be completely normal. Rest of the handicapped babies will be a great burden for the parents and the nation. While the team is doing resuscitated efforts, somebody must counsel the relatives and if the relatives agree when the fetal heart and resuscitation are not coming back, the attempt should be given up

   

TA Joseph, SP Pyati, (Cook County Children’s Hosp, Chicago; Finch Univ, North Chicago; Univ of Illinois, Chicago)


Neonatal Early-Onset Escherichia coli Disease: The Effect of Intrapartum Ampicillin.


Arch Pediatr Adolesc Med 152: 35-40, 1998.

  


One of the most organisms responsible for sepsis during the newborn period is E.coli. Ampicillin has been increasingly used by obstetricians for intrapartum chemoprophylaxis for group B streptococcal disease. However the consequences of this practice are unknown. The clinical characteristics and outcomes associated with early-onset neonatal E.coli disease were delineated, and the effect of increased use of intrapartum ampicillin during recent years on the rate of early-onet E.coli infection and case fatalities was assessed.

  


Methods: Intrapartum ampicillin use increased since 1988 and infection and case fatality rates were compared before 1988 and afterwards.

   


Results: Early-onset E.coli infection was diagnosed in 30 of the 61498 liver births, and the infected neonates had a clinical syndrome that was indistinguishable from early-onset group B streptococcal infection. The single most frequent finding in 73% of the infected neonates was respiratory distress.

    


Ampicillin resistant infection was found in a higher proportion of neonates born to ampicillin treated women. In mothers with sensitive organisms and resistant organisms, the difference between the prevalence of intrapartum fever was significiant in proportionate cases. Ampicillin resistant organisms caused all 6 early onset E.coli related deaths; of these 4 of the 6 mothers received intrapartum ampicillin.

    


Conclusion : There has been a shift of early-onset E.coli infection from a less fulminant disease caused by ampicillin-sensitive organisms to a more fulminant disease caused by organisms that are resistant to ampicillin.

    


Editorial comment: The concern that attempts to eradicate the group B streptococcus (GBS) will result in the reemergence of resistant gram-negative organisms may be well justified. 

     


Towers et al have also written on this particular subject and they observed that the incidence of early-onset neonatal sepsis with group B streptococci decreased during their study periods, whereas the incidence of early-onset sepsis with non-group B streptococcal organisms, especially E.coli, increased. It is important that the recommendations for the use of intrapartum penicillin G, rather than ampicillin, for prophylaxis against group B streptococci be followed.

    

M
Adhikhari, T Pillay, DG Pillay (Univ of Natal, Kwa-Zula Natal, South Africa)


Tuberculosis in the Newborn: An Emerging Disease.


Pediatr Infect Dis J 16: 1108-1112, 1997.

   


Introduction: Despite the global increase of tuberculosis, which has been fueled, in part, by the HIV infection pandemic, it is rare to see tuberculosis in the perinatal period.

  


Methods: Seventy-seven neonates, with a differential diagnosis of tuberculosis, were studied during a 1-year period in a province with epidemics of tuberculosis and HIV infection. For neonates with a confirmed diagnosis of tuberculosis, the clinical profiles, short-term outcome, and relationship to maternal tuberculosis and HIV infection were determined.

  


The clinical characteristics of tuberculosis and HIV coinfection in the adult have been well characterized. In contrast to immunologically normal patients, in whom tuberculosis infection remains subclinical in the overwhelming majority, HIV infected patients develop a clinical disease much more frequently. There is a marked predilection for extra pulmonary spread of the mycobacteria, particularly to the lymph nodes, central nervous system, bone marrow, and genitourinary and gastrointestinal tracts.

   


Conversely, it also has been noted that tuberculosis can accelerate clinical deterioration in the HIV-infected patient independent of the morbidity caused by the tuberculosis infection itself.

  


The cause for this deterioration are speculative, but cytokines produced after M tuberculosis infection, particularly tumor necrosis factor and interleukin-1, promote HIV replication in vitro and may do so in vivo as well.

  


In the United States there is aggressive screening for HIV infection among tuberculosis clinic patients, and tuberculosis screening among HIV clinic patients; this results in early diagnosis and treatment of both. Moreover, intragestational prophylaxis to prevent vertical transmission of HIV to the newborn is highly effective and has resulted in a dramatic diminution in the number of neonates born with HIV and its resultant severe immunologic impairment.

  

ME O’Connor, W Schmidt, et al (Case Western Reserve Univ, cleveland, Ohio)


Relaxation Training and Breast Milk Secretory IgA


Arch Pediatr Adolesc Med 152:1065-1070, 1998.



A study was undertaken to determine whether relaxation training and suggestion to breast feeding women would increase the secretory IgA (sIgA) levels in their breast milk to improve the immunity of breast-fed infants.



It was concluded that breast milk sIgA levels were increased with self-reported stress. sIgA levels were inversely related to success at relaxation in the group learning to relax.



Editorial comments: However, as all new mothers are sleep deprived and stressed, it should be of some comfort and consolation for them to learn that this is beneficial for their babies.

  

L
Verma, F Macdonald. P Leedham, et al (Birmingham Heartlands Hosp, England)


Rapid and Simple Prenatal DNA Diagnosis of Down’s Syndrome.


Lancet 352: 9-12, 1998.



Since the 1970s, cultured amniotic fluid cells obtained by amniocentesis at around 16 weeks of gestation have been used for the prenatal diagnosis of down’s syndrome by Karyotyping. This approach requires 10 mL of fluid, and it takes an average of 15 days for the results to be known. A new approach involves polymerase chain reaction (PCR) amplification of small-tandem-repeat markers located on chromosome 21 and analysis with fluorescence based methods. With this technique, results are available on the same day and only a small amount of fluid is required. The use of this approach for the diagnosis of trisomy 21 was investigated in a series of more than 2000 samples of amniotic fluid



Two DNA markers gave an informative and correct result in 2,083 of 2,139 samples (97.4%), in which 30 fetuses were identified as having trisomy 21 Down’s syndrome and 2,053 fetuses were identified as normal. In 32 of 41 other clear samples, an extra marker was informative. With these 3 markers, a total of 99.6% informative results were achieved. No false negative or false positive results were seen.

  


Authors conclude -For improved prenatal diagnosis of Down’s syndrome, the PCR-based DNA diagnostic test has great potential. The advantage is that results may be available within a day.

  


The PCR has revolutionized the practice of molecular genetics. Similar techniques could be employed simultaneously for the prenatal diagnosis of other common aneuploidies such as trisomy 13 and trisomy 18. PCR based prenatal diagnosis of trisomy 21 (as an adjunct to conventional cytogenetic analysis) is cost-effective and that the tremendous time saving. Rapid prenatal diagnosis of trisomy 21 through fluorescence in situ hybridization (FISH) is already a relatively well-established procedure in the United States.

    

Ymd Lo, NM Hjelm, C Fidler, et al (Univ of Hong Kong, China; John Radcliffe Hosp, Oxford, England)


Prenatal Diagnosis of Fetal RhD Status by Molecular Analysis of Maternal Plasma.


N Engl J Med. 339: 1734-1738, 1998.

  


Rhesus (Rh) isoimmunization still occurs, despite the widespread use of Rh immune globulin prophylaxis in RhD negative pregnant women. It would be useful to determine the RhD status of these infants because no further testing or therapeutic procedures would be necessary if the infants were RhD-negative. The feasibility of fetal RhD genotyping with the use of fetal DNA extracted from plasma samples from RhD negative pregnant women was assessed.

  


Method: The study included 57 RhD negative pregnant women and their singleton fetuses: 12 were in their first trimester; 30 were in their second trimester; and 15 were in their third trimester. An analysis was conducted for the RhD gene with a PCR test sensitive enough to detect the RhD gene in a single cell from DNA extracted from maternal plasma. Serologic analysis of cord blood or PCR analysis of amniotic fluid was used to determine fetal RhD status.

  


Results : The results of RhD PCR analysis of maternal plasma DNA were completely concordant with the results of serologic analysis in the samples obtained from women in their second or third trimester of pregnancy. Two of the maternal plasma samples collected in the first trimester contained no RhD DNA, but the fetuses were RhD-positive. The other 10 samples were found to be concordant; 7 were RhD-positive and 3 were RhD negative.

  


Conclusion: Noninvasive fetal RhD genotyping can be performed rapidly and reliably with the use of maternal plasma at the beginning of the second trimester of pregnancy. Not only is the method is reliable but also rapid.

    

TD Shipp, BR Benacerraf (Massachusetts General Hospital, Boston; Brigham and Women’s Hospital, Boston; Harvard Med School, Boston)


The Significance of Prenatally Identified Isolated Clubfoot: Is Amniocentesis Indicated?


Am J Obstet Gynecol 178:600-602, 1998.

  


Most fetuses with clubfoot have other malformations, often associated with karyotypic abnormalities.

   


Patients: The 9-year review included 87 fetuses with isolated clubfoot identified on prenatal Ultrasound. Follow-up information was available on 68 fetuses. At birth, 38 fetuses were correctly identified as having bilateral clubfoot and 15 as having unilateral clubfoot. Eight fetuses with a ultrasound diagnosis of clubfoot were found to be normal at birth. In utero karyotyping was performed on 34 fetuses, 4 of which had abnormal karyotypes. The abnormal karyotypes identified were 47 XXY, 47 XXX trisomy 18, and trisomy 21.

   


The authors conclude that a 6% incidence of karyotypic abnormalities among fetuses with a ultrasound finding of isolated clubfoot was found. These fetuses should be karyotyped even if clubfoot is the only apparent congenital anomaly. Ultrasound used prenatally for the detection of clubfoot has a false-positive rate of 12%; the false-negative rate is unknown.

   


Budorick et al report on the value of 3-dimensional ultrasound of the fetal distal lower extremity, normal and abnormal. Three-dimensional ultrasound improves one’s ability to evaluate the lower limb.

      

R M Silver, T F Porter, W Branch, et al (Salt Lake City, Utah)

Neonatal alloimmune thrombocytopenia: Antenatal management

Am J Obstet Gynecol May 2000; 182: 1233-8

  


Objective: The optimal management of pregnancies at risk for neonatal thrombocytopenia is debated. Proposed management includes the administration of intravenous immunoglobulin and serial determination of the fetal platelet count. The aims of our study were to determine the effectiveness and likely mechanism of action of intravenous immunoglobulin and to evaluate the safety of cordocentesis in cases of neonatal alloimmune thrombocytopenia.

   


Study Design: Eighteen mother-infant pairs were studied. All were at risk for neonatal alloimmune thrombocytopenia on the basis of delivery of a previously affected infant and confirmation of specific maternal antiplatelet antibodies. The pertinent antigen was HPA-1a in 13 cases, HPA-3a in 2 cases, and undetermined in 3 cases. Serial cordocenteses were used to determine fetal platelet counts. If the platelet count was <50,000/mL before 37 weeks” gestation, treatment was initiated with intravenous immunoglobulin administered to either the fetus (n=2) or the mother (n=8). In 3 cases fetal and maternal immnoglobulin G levels were determined before and after treatment.

  


Results : Seven (39%) fetuses had adequate platelet counts, were not treated, and were delivered with normal platelet counts. Eleven (61%) fetuses were thrombocytopenic. Eight thromboctytopenic infants were treated with maternally administered intravenous immunoglobulin. In 6 (75%) of 8 cases the fetal platelet count increased after administration of intravenous immunoglobulin, but 2 fetuses remained severely thrombocytopenic. Two thrombocytopenic fetuses were treated with intravenous immunoglobulin infusion directly into the umbilical vein; both remained thrombocytopenic. Moreover, fetal immunoglobulin G levels did not correlate well with the response to intravenous immunoglobulin. Two (5.3%) of 38 cordocenteses were complicated by hemorrhagic complications, necessitating immediate cesarean delivery despite the use of prophylactic platelet transfusion in one case.

   


Conclusion: Severe fetal alloimmune thrombocytopenia does not always occur in subsequent fetuses. Thus either fetal antigen status or platelet counts or both of these are necessary to determine whether treatment is needed. The effect of intravenous immunoglobulin on raising the fetal platelet count is inconsistent and appears to be caused by maternal or placental factors rather than a direct inhibition of fetal platelet destruction by immunoglobulin. The risk of hemorrhagic complications from cordocentesis in pregnancies complicated by neonatal alloimmune thrombocytopenia is higher than generally appreciated and is not always avoided by platelet transfusion at the time of the procedure.

       

T K Lau, T Y Leng, et al (Shatin, Hong Kong)

Effect of external cephalic version at term on fetal circulation

Am J Obstet Gynecol, May 2000, 182 : 1239-42

    


Objective: The authors sought to investigate the sub-clinical effect of external cephalic version on fetal circulation.

   


Study Design : A prospective observational study was conducted on 136 subjects who had external cephalic version at or beyond 36 weeks of gestation without clinical complication. Doppler ultrasonographic studies of the umbilical and middle cerebral circulations were performed before and after the external cephalic version. The following Doppler indexes were measured (1) the pulsatility index of the umbilical artery, which represents disturbance of placental circulation, and (2) the pulsatility index of the fetal middle cerebral artery, which represents fetal response. The Wilcoxon signed rank test was used for all statistical analyses.

   

Results: There was no significant difference in pulsatility index of the umbilical artery before and after external cephaclic version (P=.674). There was a statistically significant reduction in the pulsatility index of the middle cerebral artery after external cephalic version (P=.029), among those in whom the external cephalic version was considered to be difficult (P=.038), and when the placenta was posteriorly located (P=.028). The reduction in pulsatility index was not related to whether the external cephalic version was successful. In all cases the Doppler indexes remained within the normal ranges, and there were no associated fetal complications.

  


Conclusion: External cephalic version was not associated with any significant disturbance of placental resistance to blood flow. Conversely, external cephalic version was associated with a significant reduction in the pulsatility index of the middle cerebral circulation, especially among the multiparous women, after a difficult procedure or in those with a posterior placenta. This probably represents a normal fetal physiologic response to manipulation of the fetal head.

Fetus-Placenta-Newborn

Lyndon M. Hill, Marijane Krohn, Noam Lazebnik, Brenda Tush, Deborah Boyles, and John J. Ursiny

The Amniotic Fluid Index in Normal Twin Pregnancies

Am J. Obstet Gynecol April 2000, Volume 182, Number 4, Pgs. 950-954



Objective -They sought to investigate the amniotic fluid index for individual gestational sacs of twin pregnancies.



Study Design – Four hundred eighty-eight patients with normal diamniotic twins were examined between 14 and 40 weeks’ gestation. The dividing membrane between twin fetuses was identified. An amniotic fluid index was then obtained for each gestational sac.



Results – The median amniotic fluid index in individual twin gestational sacs rises slowly from 14 to 16 weeks’ gestation to 23 to 28 weeks’ gestation and then gradually declines. The median amniotic fluid index values by gestational age for twin A and twin B are not statistically different. Although twin pregnancies have a slightly lower median amniotic fluid index value than singleton pregnancies, the difference is also not statistically significant.



Conclusion – Individual amniotic fluid indices can be obtained in twin pregnancies, and the values are comparable with those of singleton gestations.

Kathryn L. Reed, and Caroline F. Anderson, [ From the Department of Obstetrics and Gynecology, Arizona Health Sciences Center ]

Changes in Umbilical Venous Velocities with Physiologic Perturbations

Am J. Obstet Gynecol April 2000, Volume 182, Number 4, Pgs. 835-840



Objective – The purpose of this study was to determine the direction of transmission of umbilical venous Doppler flow velocity changes in human fetuses.



Study Design – Strip chart recordings of simultaneously measured umbilical arterial and venous velocities were examined at two sites in the umbilical cord, one near the fetus [ proximal] and one near the placenta [distal]. Fetuses with venous pulsations or breathing episodes were included. At both locations time from venous pulsation to arterial systole was measured in fetuses with venous pulsations and duration of phase delay between arterial diastolic velocity minimum and venous velocity minimum was measured in fetuses with breathing episodes.



Results – In 21 fetuses with venous pulsations the pulsations occurred earlier in the cardiac cycle at proximal sites [0.12 + 0.04 second before systole] and later at distal sites [0.02 + 0.04 second before systole; p<.001]. Phase delays in venous velocities in the 5 fetuses with breathing episodes were also longer at distal sites than at proximal sites [P<.011]. 



Conclusion – changes in umbilical venous velocities occurred earlier at sites that were closer to the fetus. These findings suggest that changes in umbilical venous velocities originate in the fetal venous system and are transmitted to, rather than from, the placenta.

Matthias David Matthias M. Walka, Bernhard Schmid, Pranav Sinha, Siegfried Veit, and Werner Lichtenegger, 

Nitroglycerin Application During Cesarean Delivery : Plasma Levels, Fetal/Maternal Ratio of Nitroglycerin, and Effects in Newborns

Am J. Obstet Gynecol April 2000, Volume 182, Number 4, Pgs. 955-961



Objective -Over the last decade, there have been several reports of successful obstetric use of nitroglycerin as a ticolytic. Nitroglycerin, which is also known 

as glycerol trinitrate, may be administered before, during, or after delivery and is well suited for use as a short-term tocolytic agent before external and internal change to extract a retained placenta or to correct a uterine inversion, as well as during cesarean delivery. 



They sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery.



Study Design – At the time of the uterine puncture incision, either 0.25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1,5, and 10 minutes after birth.



Conclusion – The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates. 



Doses between 0.05 mg and 1.85 mg glycerol trinitrate have been used successfully for various indications, both subpartum and postpartum, and doses have been applied intravenously, as patches, and as sublingual sprays.



The marked difference between venous and arterial levels of glycerol trinitrate and its metabolites in the umbilical cord indicates that the process of nitrate breakdown is already functioning well before birth.



They conclude that there is no evidence of major risk to the neonate from administration of an intravenous bolus of 0.25 or 0.5 mg glycerol trinitrate to the mother during a cesarean delivery.