Neurobehavioural Outcomes in Late Preterm Neonates
Condition: Pre-Eclampsia
MeSH terms: Eclampsia; Pre-Eclampsia
Study type: Observational

Summary: 
      Hypertensive disorders are the most common medical complications in pregnancy and major
      causes of maternal, fetal, and neonatal morbidity and mortality. Fifty percent of
      hypertensive disorders of pregnancy are defined as pre eclampsia, the most important
      manifestation of the disease.

      Preeclampsia is also a significant risk factor in the development of IUGR and represents the
      most common cause of IUGR in the nonanomalous infant. The incidence of thrombocytopenia,
      neutropenia and Bronchopulmonary dysplasia is also increased in neonates with preeclampsia.

      The neurodevelopmental outcomes infants exposed to preeclampsia are highly variable. The
      study by Gray et al showed that preeclampsia is associated with a decreased risk of cerebral
      palsy. They also found a protective effect of maternal preeclampsia on cerebral palsy
      regardless of exposure to magnesium sulfate. However, contrary to this, study conducted by
      Shao-Wen Cheng et al has showed that infants born to pre-eclamptic mothers had lower MDI
      scores at 24 months of age (P= 0.04) as compared to infants without maternal pre-eclampsia.
      The study by Szymonowicz et al showed that neonates born to pre-eclamptic mothers had a
      significantly lower mean mental developmental index, and significantly more of these children
      had one or more impairments compared with the control group at 2 years of age. The
      neurodevelopmental outcomes in neonates born to preeclamptic mothers therefore remain
      inconclusive. Recently the role of neurobehaviour being evaluated early at 37-40 weeks of CGA
      is being predicted as an useful adjunct to the 12-18 month full neurodevelopmental
      assessment. This assumes significance in the context of initiation of early stimulation and
      objectivised individual developmental rehabilitation regimens for these infants.
    

Detailed description: 
      Preeclampsia is a multiorgan, heterogeneous disorder of pregnancy associated with significant
      maternal and neonatal morbidity and mortality.

      The incidence of preeclampsia is about 5% to 10% of all pregnancies, with higher rates
      reported in first pregnancies, twin pregnancies, and in women who have had previous pre
      eclampsia. Fifty percent of hypertensive disorders of pregnancy are defined as preeclampsia,
      the most important manifestation of the disease.

      While preeclampsia complicates 6%-10% of all pregnancies in the United States, the incidence
      is believed to be even higher in underdeveloped countries.

      Perinatal mortality rates from range from 59 in 1,000 in developed countries to more than 300
      in 1,000 in low income countries.

      Preeclampsia and eclampsia accounts for 24% of all maternal deaths in india. Diagnostic
      criteria for preeclampsia Blood pressure Greater than or equal to 140 mm hg systolic or
      greater than or equal to 90 mm hg diastolic on two occasions at least 4 hours apart after 20
      weeks of gestation in a woman with previously normal blood pressure Greater than or equal to
      160 mm hg systolic or greater than or equal to 110 mm hg diastolic , hypertension can be
      confirmed within a short interval ( minutes ) to facilitate timely antihypertensive therapy
      And Proteinuria Greater than or equal to 300 mg per 24 hour urine collection ( or this amount
      extrapolated from a timed collection ) or Protein / creatinine ratio greater than or equal to
      0.3 mg/dl Dipstick reading of 1+( used only if other quantitative methods not available )

      Or in the absence of proteinuria, new onset hypertension with the new onset of any of the
      following:

      Thrombocytopenia Platelet count less than 100000/ microliter Renal insufficiency Serum
      creatinine concentrations greater than 1.1 mg/dl or a doubling of the serum creatinine
      concentration in the absence of other renal disease Impaired liver function Elevated blood
      concentrations of liver transaminases to twice normal concentration Pulmonary edema Cerebral
      or visual symptoms

      LATE PRETERMS: A SPECIAL COHORT

      Definition:

      Premature infants ( born at < 37 completed weeks gestation) are categorized into subgroups

        -  Very preterm (<32 completed weeks)

        -  Moderately preterm (between 32 and 33 completed weeks)

        -  Late preterm (between 34 and 36 completed weeks) Late preterm birth is an accepted term
           used for infants born at 34 0/7 to 36 +6/7 weeks gestation. This group was initially
           referred to as near term, but misleading implications of maturity has prompted the name
           change to late preterm.

      Magnitude of late preterm births Prematurity is a leading cause of morbidity and mortality
      globally. Advances in medicine and technology have shifted the distribution of births away
      from term/post-term towards earlier gestations.

      The percentage of live births in the United States that were born late preterm increased
      between 1990 and 2006 from 7.3% to 9.14% , a 25% increase.

      This increase accounted for 84% of the increase in the prematurity during that same 16 year
      period. Thus this group of late preterms account for the maximum burden of premature births.

      Etiology of late preterm births Preterm deliveries are divided into two groups

        -  The first group: Spontaneous late preterm births (premature labor with intact membranes
           or premature rupture of membranes) where there is limited control on preventing the
           birth and the focus lies in a better understanding of the management of the neonate in
           the perinatal period.

        -  The second group includes premature babies born after the induction of labor or
           performance of a cesarean section for maternal or fetal indications.

      Consequences of late preterm births Acute Medical Morbidities and Mortality

      This group is characterized by physiological immaturity with limited compensatory responses
      to extrauterine environment compared to term infants. They have greater risk than term babies
      for morbidities and mortalities such as:

        -  Temperature instability

        -  Hypoglycemia

        -  Respiratory distress

        -  Apnea

        -  Jaundice

        -  Feeding difficulties

        -  Dehydration

        -  Suspected sepsis

        -  Neurologic disorder and/or death The risk of death and/or a severe neurologic disorder
           defined by ischemic encephalopathy,Grade 3 or 4 IVH, cystic periventricular leukomalacia
           and/or seizures increased to 1.7% at 34 Weeks gestation as compared to 0.15% at 38 weeks
           gestation.

      Long-term morbidities in late preterms Long-term outcomes affected by late preterm involve
      school performance, behaviour problems, social and medical disabilities, and mortality.
      Although the absolute risk of poor long-term outcomes in infants born late preterm are small,
      the risks are significantly greater than if born at 39-40 week gestation.Medical and social
      morbidities increase with decreasing gestational age. In cohort of 903,402 Norwegian infants
      born alive without congenital anomalies and followed through early adulthood, infants born
      late preterm had significant higher risks for cerebral palsy; cognitive dysfunction;
      schizophrenia; disorders of psychological development, behavior, and other major
      disabilities.

      EFFECTS OF PREECLAMPSIA ON LATE-PRETERM INFANT OUTCOMES Risk of Fetal Demise/Stillbirth
      Severe preeclampsia represents significant risk factor for intrauterine fetal demise, with
      estimated stillbirth rate of 21 per 1000 20. In the setting of severe preeclampsia, the risk
      of fetal death outweighs the potential benefits of pregnancy prolongation. However, in cases
      of mild preeclampsia, the risk of fetal demise is over 50% less than pregnancies with severe
      preeclampsia (stillbirth rate of 9 per 1000) Intrauterine Growth Restriction (IUGR)
      Preeclampsia, a condition characterized by decreased uteroplacental blood flow and ischemia,
      is a significant risk factor in the development of IUGR and represents the most common cause
      of IUGR in the nonanomalous infant.

      Hematologic Effects Maternal preeclampsia can result in neonatal thrombocytopenia, typically
      defined as a platelet count less than 150,000/uL. Severity of thrombocytopenia related to
      preeclampsia is highly variable, with a small percentage of infants developing severe or
      clinically significant thrombocytopenia (<50,000/uL). In addition to the well-described
      effects of preeclampsia on platelets, neonates delivered to women with preeclampsia have a
      50% incidence of neutropenia (defined as absolute neutrophil count less than 500).

      Bronchopulmonary Dysplasia (BPD) The study by Hansen et al shows that maternal preeclampsia
      is, associated with an increased risk for development of BPD, even after adjusting for
      gestational age, birth weight, and other clinical confounders (OR 2.96, 95% CI 1.17-7.51)
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        SAMPLE SIZE 60 intramural neonates divided in a group of 30 each. STUDY SUBJECTS Thirty
        late-preterm infants born to mothers with preeclampsia ---late preterms defined as infants
        born between 34 0/7 weeks and 36 6/7 weeks of gestation.

        CONTROL SUBJECTS Thirty late preterm infants born to mothers without preeclampsia.
      
Keywords: NAPI; late preterm