REVIEW

Maternal preeclampsia effects on newborn – review

 Efectele preeclampsiei materne asupra nou-născutului – revizuire

First published: 12 aprilie 2022

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/Pedi.65.1.2022.6277

Abstract

Nowadays, preeclampsia is a common condition, with up to 5-10% of pregnancies being associated with this disease. In addition to the devastating effects preeclampsia can have on the pregnant woman, by increasing her risk of thromboembolic events, intracerebral hemorrhage, HELLP syndrome, eclampsia or damage to other organs, the fetus is also at risk if the disease is not diagnosed and controlled on time. We present a review of the effects of maternal pre­eclampsia on the newborn. Due to the placental hypo­per­fusion caused by preeclampsia, the fetus may have res­tricted intrauterine growth, iatrogenic premature birth, oli­go­amnios, neonatal respiratory distress syndrome, bron­cho­pul­monary dysplasia, intraventricular hemorrhage, neu­ro­developmental sequelae, including cerebral palsy, gas­tro­in­tes­tinal disorders, such as necrotizing enterocolitis, sepsis or even intrauterine death. Thus, the diagnosis and monitoring of this pathology as early as possible become an important obligation of the obstetrician, as these are crucial for the benefit of both the mother and the newborn. The treat­ment of preeclampsia also represents a challenge, given the fact that, until now, there are no therapeutic management protocols, and all drug options come with the associated reactions or complications, delivery representing the only curative outcome. 
 

Keywords
preeclampsia, gestational hypertension, newborn, intrauterine growth restriction, cerebral palsy, prematurity

Rezumat

Preeclampsia este o afecţiune frecventă în prezent, până la 5-10% dintre sarcini fiind asociate cu această boală. Pe lângă efec­te­le devastatoare pe care preeclampsia le poate avea asu­pra gravidei, prin creşterea riscului acesteia de apariţie a eve­ni­men­te­lor tromboembolice, de hemoragie intracerebrală, sin­drom HELLP, eclampsie sau de afectare a altor organe, fătul este de asemenea expus, dacă boala nu este diagnosticată şi con­tro­la­tă la timp. Prezentăm o trecere în revistă a efectelor pre­eclamp­siei materne asupra nou-născutului. Astfel, din cau­­za hipoperfuziei placentare cauzate de preeclampsie, fă­­tul poate avea o creştere intrauterină restricţionată, naştere pre­­ma­­tu­ră de origine iatrogenă, oligoamnios, sindrom de de­tre­să res­pi­ra­to­rie neonatală, displazie bronhopulmonară, he­­mo­­ra­gie intraventriculară, sechele de neurodezvoltare, in­­clu­siv pa­ra­li­zie cerebrală, tulburări gastrointestinale, en­te­ro­­co­­lită ul­ce­ro­ne­crotică, chiar şi moarte intrauterină. Astfel, diag­nos­ticul şi monitorizarea cât mai precoce ale acestei pa­to­lo­gii devin o obligaţie importantă a medicului obstetrician, fiind cruciale atât pentru mamă, cât şi pentru nou-născut. Tra­ta­men­tul preeclampsiei reprezintă, de asemenea, o provocare, având în vedere că până în prezent nu există protocoale de manage­ment terapeutic şi toate opţiunile medicamentoase vin cu reac­ţii­le sau complicaţiile asociate, doar naşterea reprezentând re­zul­tatul curativ.
 

1. Introduction

Classically, the American College of Obstetrics and Gynecology (ACOG) defines preeclampsia as the presence of hypertension and proteinuria occurring after 20 weeks of gestation in a previously normotensive patient. However, pregnant women frequently also show other biochemical changes, leading up to the development of proteinuria, such as low platelets and/or elevated liver enzymes.

Preeclampsia is a common pregnancy disease, since between 6% and 10% of all pregnancies develop this complication(1,2). This highly variable disorder represents a leading cause of maternal and fetal morbidity and mortality(3-10). The high mortality is also caused by the need for premature delivery in many cases, especially in those where preeclampsia sets in early during the pregnancy.

There are two variants of preeclampsia, depending on the onset of the disease: early-onset preeclampsia (before 34 weeks of gestation) and late-onset preeclampsia (after 34 weeks of gestation). While the first subtype is less common, it has much stronger effects on the pregnant woman and the fetus, and it also has a much higher risk of perinatal and maternal death(11,12).

2. Pathophysiology

There are two stages required for the onset of preeclampsia, abnormal placentation in the first trimester, followed by an accumulation of maternal manifestations in the second and third trimesters, based on excess angiogenic factors(12).

The exact pathophysiological mechanism leading to the development of preeclampsia remains controversial and unclear. However, the main common belief is that uteroplacental ischemia, due to oxidative stress, abnormal natural killer cells and transformation of the spiral arteries, drives the hypertensive, multiorgan failure response(13,14). This endometrial dysfunction and inflammation lead to hypoperfusion of the fetoplacental unit.

Another possibility is the alteration of both innate and adaptive immune processes due to a genetic predisposition to preeclampsia. The polymorphism of genes encoding inflammatory factors, activated by placental insufficiency or hypoxia, may explain the aberrant immune response specific to this pathology(15).

Nevertheless, it is unanimously accepted that preeclampsia consists in a status of imbalance between circulating angiogenic and antiangiogenic factors. Preeclampsia is characterized by decreased concentrations of the proangiogenic vascular endothelial growth factor and placental growth factor and increased concentrations of antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 and soluble endoglin(16,17).

3. Diagnosis

The diagnosis of preeclampsia is generally made after 20 weeks, being classified as mild, moderate or severe preeclampsia(18).

Mild preeclampsia involves an elevated blood pressure less than 160 mmHg (systolic) and/or 120 mmHg (diastolic) and proteinuria with higher values than 300 mg, but less than 5 g per day.

Severe preeclampsia is characterized by an elevated blood pressure higher than 160 mmHg (systolic) and/or 110 mmHg (diastolic) and proteinuria equal or higher than 5 grams per day(19). Severe preeclampsia is sometimes associated with thrombocytopenia (less than 100,000/uL), oliguria (less than 500 mL per day) or with pulmonary edema.

4. Management

The only effective cure for preeclampsia is delivery, and until delivery the main important target is to control the blood pressure. Although it does not cure the pathology, blood pressure control leads to a decrease in the risk of associated maternal cerebrovascular events and to an extension of the gestation period as close as possible to the term.

However, the administration of antihypertensives is often delayed due to their well-known effect of decreasing uteroplacental irrigation, leading to intrauterine growth restriction or fetal bradycardia(20).

Antihypertensives such as methyldopa, labetalol or nifedipine are most commonly used. Each antihypertensive drug comes with its own pregnancy-associated risks(21,22).

For example, atenolol has been associated with fetal growth restriction, while labetalol is associated with neonatal hypoglycemia and bradycardia(23).

Nifedipine and methyldopa are considered the safest antihypertensives for use during pregnancy.

5. Effects of preeclampsia on newborn

5.1. Fetal growth restriction

Preeclampsia, characterized by decreased uteroplacental blood flow and ischemia, is the most common cause of intrauterine growth restriction. Severe preeclampsia is a well-known factor associated with reduced birth size, while mild preeclampsia is less frequently associated with this condition(24,25).

It is well known how the circulation responds to hypoxia, by centralizing the circulation to protect the noble tissues (“brain sparing”). The fetal circulation performs the same process and, thus, during control ultrasounds, a cranial circumference can be observed which increases accordingly, while in the case of femoral length or abdominal circumference, a stagnation of the parameters is noted, due to the existing vasoconstriction at that level.

When preeclampsia develops early, by considering fetal biometrics and gestational age, the woman’s counselor must be realistic, in accordance with the chances of survival of the fetus. Thus, if in the case of a pregnancy under 24 weeks, with an estimated fetal weight less than 500 grams, diagnosed with preeclampsia and requiring delivery, the prognosis of the newborn is unfavorable.

In addition to biometrics, the Doppler velocimetry of three fetal vessels – middle cerebral and umbilical arteries and ductus venosus – is also recommended in order to provide information on the downstream peripheral vascular impedance of the placenta. It has been shown that absent or reversed end-diastolic flow in the umbilical artery is correlated with poor perinatal outcomes(26).

When brain sparing is present, a reduction in cerebral flow resistance can be observed, which can be characterized as a decrease in the Doppler indices of the middle cerebral arteries. The normalization of these parameters occurs in severe and terminal cases of fetal growth restriction.

Fetal growth restriction is common especially in early-onset preeclampsia. The associated risk of intrauterine death is 15 times higher(27), in direct correlation with the severity of the Doppler velocimetry abnormalities(28) and independent of the gestational age(29).

Guidelines suggest that fetuses with late-preterm intrauterine growth restriction should be delivered when there is any evidence of maternal hypertension(30).

5.2. Bronchopulmonary dysplasia (BPD)

There are several hypotheses for preeclampsia being a risk factor for BPD. Preeclampsia is also a predisposing condition for a restriction in fetal angiogenesis, due to the reduced blood flow to the fetoplacental level, through hypoxia and ischemia(31).

The “vascular hypothesis of BPD” suggests that preeclampsia can alter critical lung-vessel interactions necessary for normal lung development, even after adjusting for birth weight and gestational age(32-34). This is due to an imbalance between pro- and antiangiogenic factors that could also impair the vascular and alveolar development of the fetal lungs(35-40).

Since delivery is the only effective treatment, preeclampsia often leads to small for gestational age and premature birth.

As with intrauterine growth restriction, cases of BPD have generally been reported in severe preeclampsia and in newborns less than 28 weeks of age(41).

5.3. Hematological effects

The proinflammatory immune state can disrupt fetal hematopoiesis, so that the hematological profile of the newborn can be badly altered. Neonatal thrombocytopenia, with a platelet count less than 150,000/uL, neutropenia, reduction in T regulatory cells and an increased cytotoxic natural killer profile were all observed in neonates born from pregnant women with preeclampsia.

Thrombocytopenia is usually identified at birth or in the first third days after delivery, in most cases with rapid resolution of no more than two weeks(42). Rarely, neonates develop severe or clinically significant thrombocytopenia (<50,000/uL)(43,44). Unfortunately, the pathophysiological process through which they develop thrombocytopenia is still unknown(45). The only mechanism indicated so far is that fetal hypoxia is a depressant status for megakaryocyte proliferation(46). These newborns have been shown to have significant megakaryocytopoiesis defects without any evidence of increased platelet destruction, thus supporting this hypothesis(47).

The incidence of neutropenia (neutrophil count less than 500) is 50% in neonates delivered to women with preeclampsia and it is usually associated with reduced numbers of circulating colony-forming unit-granulocyte macrophage (CFU-GM)(48,49). The fetal bone marrow production of the myeloid lineage is inhibited by uteroplacental insufficiency(50).

This is why an early neonatal hematological screening should be performed in these cases, in order to decrease mortality and improve the growth and development of the baby.

5.4. Neurodevelopmental spectrum diseases

Children exposed to preeclampsia have highly variable neurodevelopmental outcomes. It was shown that maternal preeclampsia has a protective effect on the brain, with a lower risk of cerebral palsy(51).

Lower risk of intraventricular hemorrhage was also suggested among infants born between 26 and 30 weeks from pregnancies diagnosed with preeclampsia(52).

When comparing through three sets of neuropsychomotor development tests – Bayley Scales of Infant Development, second edition (BSDI-II), Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) – children of the same age, from normal pregnancies, versus children from mothers with preeclampsia, both groups were shown to have similar neuropsychological and intellectual development at 12 months and at 18 months, with the group undergoing preeclampsia having higher scores, therefore better intellectual development(53).

Conclusions

The early diagnosis and treatment of preeclampsia are a necessity for both the pregnant woman and the newborn. The effects of this condition on the woman are described in detail, while those on the newborn remain in the study stage.

Preeclampsia leads to a much higher risk of death in utero, as well as to the restriction of intrauterine growth, bronchopulmonary dysplasia, thrombocytopenia, or neutropenia. The medium- and long-term consequences on the development of the newborn still remain to be studied, as this specific uteroplacental insufficiency and the hypoxic status in which the conception product develops can have effects not only in the perinatal period, but also repercussions in the adult life.  

 

Conflict of interests: The authors declare no con­flict of interests.

 

Bibliografie

  1. Odendaal HJ, Pattinson RC, Bam R, Grove D, Kotze TJ. Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks’ gestation: a randomized controlled trial. Obstet Gynecol. 1990 Dec;76(6):1070-5.

  2. Sibai BM. Diagnosis and management of gestational hypertension and pre­eclampsia. Obstet Gynecol. 2003 Jul;102(1):181-92. doi: 10.1016/s0029-7844(03)00475-7.

  3. Caritis S, Sibai B, Hauth J, Lindheimer M, VanDorsten P, Klebanoff M, Thom E, Landon M, Paul R, Miodovnik M, Meis P, Thurnau G, Dombrowski M, McNellis D, Roberts J. Predictors of pre-eclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Am J Obstet Gynecol. 1998 Oct;179(4):946-51. doi: 10.1016/s0002-9378(98)70194-2.

  4. Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ. 1994 Nov 26;309(6966):1395-400. doi: 10.1136/bmj.309.6966.1395.

  5. Ness RB, Roberts JM. Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications. Am J Obstet Gynecol. 1996 Nov;175(5):1365-70. doi: 10.1016/s0002-9378(96)70056-x.

  6. Backes CH, Markham K, Moorehead P, Cordero L, Nankervis CA, Giannone PJ. Maternal preeclampsia and neonatal outcomes. J Pregnancy. 2011;2011:214365. doi: 10.1155/2011/214365.

  7. Obaid KA, Maan BK, Ghasaq MB. Effect of maternal hypertension on neonatal outcome in Diyala Province, Iraq. Diyala Journal of Medicine. 2013;5(2):68-73.

  8. Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001 Jan 6;357(9249):53-6. doi: 10.1016/s0140-6736(00)03577-7.

  9. Roberts JM, Redman CW. Preeclampsia: more than pregnancy-induced hypertension. Lancet. 1993 Jun 5;341(8858):1447-51. doi: 10.1016/0140-6736(93)90889-o. Erratum in: Lancet. 1993 Aug 21;342(8869):504.

  10. Morgan MA, Thurnau GR. Pregnancy-induced hypertension without proteinuria: is it true preeclampsia? South Med J. 1988 Feb;81(2):210-3. doi: 10.1097/00007611-198802000-00017.

  11. Barton JR, O’Brien JM, Bergauer NK, Jacques DL, Sibai BM. Mild gestational hypertension remote from term: progression and outcome. Am J Obstet Gynecol. 2001 Apr;184(5):979-83. doi: 10.1067/mob.2001.112905.

  12. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005 Jun 10;308(5728):1592-4. doi: 10.1126/science.1111726.

  13. Palei AC, Spradley FT, Warrington JP, George EM, Granger JP. Pathophysiology of hypertension in pre-eclampsia: a lesson in integrative physiology. Acta Physiol (Oxf). 2013 Jul;208(3):224-33. doi: 10.1111/apha.12106.

  14. Zhou Y, Damsky CH, Fisher SJ. Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? J Clin Invest. 1997 May 1;99(9):2152-64. doi: 10.1172/JCI119388.

  15. Hakim J, Senterman MK, Hakim AM. Preeclampsia is a biomarker for vascular disease in both mother and child: the need for a medical alert system. Int J Pediatr. 2013;2013:953150. doi: 10.1155/2013/953150.

  16. Mustafa R, Ahmed S, Gupta A, Venuto RC. A comprehensive review of hypertension in pregnancy. J Pregnancy. 2012;2012:105918. doi: 10.1155/2012/105918.

  17. Hakim J, Senterman MK, Hakim AM. Preeclampsia is a biomarker for vascular disease in both mother and child: the need for a medical alert system. Int J Pediatr. 2013;2013:953150. doi: 10.1155/2013/953150.

  18. Wagner LK. Diagnosis and management of preeclampsia. Am Fam Physician. 2004 Dec 15;70(12):2317-24.

  19. Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol. 2003 Jul;102(1):181-92. doi: 10.1016/s0029-7844(03)00475-7.

  20. Magee LA, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy KE, Menzies J, Sanchez J, Singer J, Gafni A, Gruslin A, Helewa M, Hutton E, Lee SK, Lee T, Logan AG, Ganzevoort W, Welch R, Thornton JG, Moutquin JM. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015 Jan 29;372(5):407-17. doi: 10.1056/NEJMoa1404595.

  21. Waterman EJ, Magee LA, Lim KI, Skoll A, Rurak D, von Dadelszen P. Do commonly used oral antihypertensives alter fetal or neonatal heart rate characteristics? A systematic review. Hypertens Pregnancy. 2004;23(2):155-69. doi: 10.1081/PRG-120028291.

  22. Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. BMJ. 1990 Sep 22;301(6752):587-9. doi: 10.1136/bmj.301.6752.587.

  23. Bateman BT, Patorno E, Desai RJ, Seely EW, Mogun H, Maeda A, Fischer MA, Hernandez-Diaz S, Huybrechts KF. Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia. Pediatrics. 2016 Sep;138(3):e20160731. doi: 10.1542/peds.2016-0731.

  24. Cnattingius S, Mills JL, Yuen J, Eriksson O, Salonen H. The paradoxical effect of smoking in preeclamptic pregnancies: smoking reduces the incidence but increases the rates of perinatal mortality, abruptio placentae, and intrauterine growth restriction. Am J Obstet Gynecol. 1997 Jul;177(1):156-61. doi: 10.1016/s0002-9378(97)70455-1.

  25. Odegård RA, Vatten LJ, Nilsen ST, Salvesen KA, Austgulen R. Risk factors and clinical manifestations of pre-eclampsia. BJOG. 2000 Nov;107(11):1410-6. doi: 10.1111/j.1471-0528.2000.tb11657.x.

  26. Wienerroither H, Steiner H, Tomaselli J, Lobendanz M, Thun-Hohenstein L. Intrauterine blood flow and long-term intellectual, neurologic, and social development. Obstet Gynecol. 2001 Mar;97(3):449-53. doi: 10.1016/s0029-7844(00)01158-3.

  27. Damodaram M, Story L, Kulinskaya E, Rutherford M, Kumar S. Early adverse perinatal complications in preterm growth-restricted fetuses. Aust N Z J Obstet Gynaecol. 2011 Jun;51(3):204-9. doi: 10.1111/j.1479-828X.2011.01299.x.

  28. Kramer MS, Olivier M, McLean FH, Willis DM, Usher RH. Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. Pediatrics. 1990 Nov;86(5):707-13.

  29. Divon MY, Haglund B, Nisell H, Otterblad PO, Westgren M. Fetal and neonatal mortality in the postterm pregnancy: the impact of gestational age and fetal growth restriction. Am J Obstet Gynecol. 1998 Apr;178(4):726-31. doi: 10.1016/s0002-9378(98)70482-x.

  30. Temming LA, Dicke JM, Stout MJ, Rampersad RM, Macones GA, Tuuli MG, Cahill AG. Early Second-Trimester Fetal Growth Restriction and Adverse Perinatal Outcomes. Obstet Gynecol. 2017 Oct;130(4):865-869. doi: 10.1097/AOG.0000000000002209.

  31. Reynolds LP, Redmer DA. Angiogenesis in the placenta. Biol Reprod. 2001 Apr;64(4):1033-40. doi: 10.1095/biolreprod64.4.1033.

  32. Abman SH. Bronchopulmonary dysplasia: “a vascular hypothesis”. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1755-6. doi: 10.1164/ajrccm.164.10.2109111c. 

  33. Bose C, Van Marter LJ, Laughon M, O’Shea TM, Allred EN, Karna P, Ehrenkranz RA, Boggess K, Leviton A; Extremely Low Gestational Age Newborn Study Investigators. Fetal growth restriction and chronic lung disease among infants born before the 28th week of gestation. Pediatrics. 2009 Sep;124(3):e450-8. doi: 10.1542/peds.2008-3249. Epub 2009 Aug 17.

  34. Hansen AR, Barnés CM, Folkman J, McElrath TF. Maternal preeclampsia predicts the development of bronchopulmonary dysplasia. J Pediatr. 2010 Apr;156(4):532-6. doi: 10.1016/j.jpeds.2009.10.018.

  35. Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009 Jun;24:147-58. doi: 10.1152/physiol.00043.2008.

  36. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005 Jun 10;308(5728):1592-4. doi: 10.1126/science.1111726.

  37. Tsatsaris V, Fournier T, Winer N. Physiopathologie de la prééclampsie [Pathophysiology of preeclampsia]. Ann Fr Anesth Reanim. 2010 Mar;29(3):e13-8. doi: 10.1016/j.annfar.2010.02.011.

  38. Thébaud B, Ladha F, Michelakis ED, Sawicka M, Thurston G, Eaton F, Hashimoto K, Harry G, Haromy A, Korbutt G, Archer SL. Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation. 2005 Oct 18;112(16):2477-86. doi: 10.1161/CIRCULATIONAHA.105.541524.

  39. Thébaud B, Abman SH. Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am J Respir Crit Care Med. 2007 May 15;175(10):978-85. doi: 10.1164/rccm.200611-1660PP.

  40. Weiler J, Tong S, Palmer KR. Is fetal growth restriction associated with a more severe maternal phenotype in the setting of early onset pre-eclampsia? A retrospective study. PLoS One. 2011;6(10):e26937. doi: 10.1371/journal.pone.0026937.

  41. O’Shea TM, Allred EN, Dammann O, Hirtz D, Kuban KC, Paneth N, Leviton A; ELGAN study Investigators. The ELGAN study of the brain and related disorders in extremely low gestational age newborns. Early Hum Dev. 2009 Nov;85(11):719-25. doi: 10.1016/j.earlhumdev.2009.08.060.

  42. Koenig JM, Christensen RD. The mechanism responsible for diminished neutrophil production in neonates delivered of women with pregnancy-induced hypertension. Am J Obstet Gynecol. 1991 Aug;165(2):467-73. doi: 10.1016/0002-9378(91)90118-b.

  43. Castle V, Andrew M, Kelton J, Giron D, Johnston M, Carter C. Frequency and mechanism of neonatal thrombocytopenia. J Pediatr. 1986 May;108(5 Pt 1):749-55. doi: 10.1016/s0022-3476(86)81059-9. 

  44. Mehta P, Vasa R, Neumann L, Karpatkin M. Thrombocytopenia in the high-risk infant. J Pediatr. 1980 Nov;97(5):791-4. doi: 10.1016/s0022-3476(80)80272-1.

  45. Brazy JE, Grimm JK, Little VA. Neonatal manifestations of severe maternal hypertension occurring before the thirty-sixth week of pregnancy. J Pediatr. 1982 Feb;100(2):265-71. doi: 10.1016/s0022-3476(82)80653-7.

  46. Weiner CP, Williamson RA. Evaluation of severe growth retardation using cordocentesis – hematologic and metabolic alterations by etiology. Obstet Gynecol. 1989 Feb;73(2):225-9.

  47. Baschat AA, Gembruch U, Reiss I, Gortner L, Weiner CP, Harman CR. Absent umbilical artery end-diastolic velocity in growth-restricted fetuses: a risk factor for neonatal thrombocytopenia. Obstet Gynecol. 2000 Aug;96(2):162-6. doi: 10.1016/s0029-7844(00)00904-2.

  48. Mouzinho A, Rosenfeld CR, Sanchez PJ, Risser R. Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection. Pediatrics. 1992 Sep;90(3):430-5.

  49. Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med. 1989 Aug 31;321(9):557-62. doi: 10.1056/NEJM198908313210901.

  50. Koenig JM, Christensen RD. The mechanism responsible for diminished neutrophil production in neonates delivered of women with pregnancy-induced hypertension. Am J Obstet Gynecol. 1991 Aug;165(2):467-73. doi: 10.1016/0002-9378(91)90118-b.

  51. Gray PH, O’Callaghan MJ, Mohay HA, Burns YR, King JF. Maternal hypertension and neurodevelopmental outcome in very preterm infants. Arch Dis Child Fetal Neonatal Ed. 1998 Sep;79(2):F88-93. doi: 10.1136/fn.79.2.f88.

  52. Shah DM, Shenai JP, Vaughn WK. Neonatal outcome of premature infants of mothers with preeclampsia. J Perinatol. 1995 Jul-Aug;15(4):264-7.

  53. Cheng SW, Chou HC, Tsou KI, Fang LJ, Tsao PN. Delivery before 32 weeks of gestation for maternal pre-eclampsia: neonatal outcome and 2-year developmental outcome. Early Hum Dev. 2004 Jan;76(1):39-46. doi: 10.1016/j.earlhumdev.2003.10.004.

Articole din ediţiile anterioare

STUDII CLINICE | Ediţia 1 / 2016

Icterul în prima lună de viaţă - un fapt banal sau o provocare medicală

Otilia Novac

În perioada primei luni de viaţă, icterul reprezintă cel mai comun semn în atenţia medicului care are în grijă nou-născutul. Coloraţia galbenă a te...

08 ianuarie 2016
STADIUL ACTUAL AL CUNOAȘTERII | Ediţia 1 / 2016

Icterele neonatale

Maria Stamatin, Andreea- Luciana Avasiloaiei

Icterul apare la nou-născut la o valoare de peste 5 mg/dl bilirubină totală, faţă de adult, la care icterul este vizibil la valori ale bilirubinei ...

06 ianuarie 2016
ACTUALITATI/UP-TO-DATE | Ediţia 1 57 / 2020

Îmbunătăţirea motricităţii fine la copiii cu nevoi speciale utilizând terapia ocupaţională

Bogdan Almăjan-Guţă, Amalia Cuceu, Petru Eugen Mergheş, Narcis Ion Văran

Terapia ocupaţională încearcă să dezvolte calitatea vie­ţii ori­cărei persoane a cărei capacitate funcţională este li­mi­tată, acest obiectiv fiind...

19 martie 2020
CLINICAL STUDIES | Ediţia 4 60 / 2020

Studiu prospectiv privind managementul durerii acute la nou-născutul cu afecţiuni chirurgicale prin corelaţia scalei de durere CRIES cu protocolul terapeutic etapizat

Valentin Munteanu, Ioana Alecsandra Munteanu, Iulia Ciongradi, Ioan Sârbu, Elena Hanganu, Bogdan A. Stana, Maria Stamatin

The last 2-3 decades have brought major changes in the management of pain in the newborn.

16 decembrie 2020