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pregnancy

pregnancy

optimising pregnancy outcomes

  • maternal age 20-35 years
  • paternal age 20-40 years
  • socioeconomic factors
  • adequate prenatal and antenatal care
  • prenatal and antenatal folate supplements
  • avoid prenatal antibiotics (other than penicillins and cephalosporins) where possible as seems these double risk of pregnancy loss in 1st 20wks1):
    • azithromycin, clarithromycin, tetracyclines, doxycycline, minocycline, quinolones, ciprofloxacin, norfloxacin, levofloxacin, sulfonamides and metronidazole
  • avoid teratogenic exposures (radiation and medications) in 1st trimester (and in some cases such as Roaccutane, prenatally)
  • avoid infections (rubella, varicella, toxoplasmosis, etc)
  • avoid maternal lifestyle factors which may predispose to fertility or pregnancy outcome problems:
  • ensure adequate and timely medical intervention is available during labour
    • the planned home births system in WA has been associated with a 20x mortality!!! 2)

fetal outcomes

1st trimester loss:

spontaneous abortions/miscarriages:
  • aetiology:
    • oocyte/sperm defects - spontaneous mutations
    • uterine implantation ability - decreases with maternal age > 35yrs
    • placental blood flow - maternal pro-thrombotic disorders
    • immunologic
    • drug/chemical/viral damage
    • genetic causes
    • a small study in 2019 suggests high levels of insulin may be toxic to placental trophoblast cells and thus perhaps insulin resistance may have a role in miscarriages, metformin may be protective 3)
  • risk of miscarriage:
    • maternal age:
      • risk of miscarriage requiring admission to hospital increases with maternal ages ~ exponentially after 25yrs:
        • < 25 yrs old: ~15% (9% if no prior aborts, ~20% if prior 1-2 aborts, 22% if prior > 2 aborts & parous, 50% if prior > 2 aborts & nulliparous)
        • 30 yrs old: ~ 18%
        • 35yrs old: ~23%
        • 40yrs old: ~35%
        • 45yrs old: ~60%
    • prior spontaneous abortions:
      • 1 abort: increases risk by ~ 40% (ie. 9% baseline risk for < 25yr old increases to ~12% risk)
      • 2 aborts: almost doubles risk (ie. 9% baseline risk for < 25yr old parous increases to ~17% risk but 23% if nulliparous)
      • > 2 aborts:
        • depends on whether nulliparous or not:
          • if nulliparous, risk increases to at least double baseline risk for age (eg. 50% for < 25yr olds, 40% for 30-40yr olds, 80% for 40-45yrolds)
          • if parous, increased risk is mainly to < 40yr olds (eg. 22% for < 25yr olds, 35% for 25-29yr olds, 32% for 30-39yr olds, 45% for 40-44 yr olds)
    • untreated coeliac disease is reported to have a 8-9x risk of recurrent miscarriages compared with treated patients but requires further study4)
    • working night shifts
      • 2 or more night shifts per week increases risk of miscarriage by 32% (Danish study 2019)

ectopic pregnancy:

  • incidence: 2.3% of all pregnancies admitted to hospital
  • risks:
    • maternal age:
      • < 25yrs old: 1.4% risk
      • 25-30yrs: 2% risk
      • 35yrs: 4% risk
      • 40yrs: 6% risk
    • tubal damage:
    • ciliary impairment - smoking, progesterone only pills
    • ovulation induction

stillbirths:

  • risks:
    • maternal age:
      • < 20 yrs: 0.5% risk
      • 20-30yrs: 0.4% risk
      • 35-39yrs: 0.5% risk
      • 40-44yrs: 0.65% risk
      • > 44yrs: 0.8% risk

congenital defects:

spontaneous mutations:

  • hydatidiform mole
  • Down's syndrome:
    • maternal age
  • achondroplasia:
    • paternal age
  • schizophrenia:
    • paternal age - age > 50yrs 2x risk
  • autism:
    • paternal age - age > 50yrs 2x risk

spina bifida / neural tube defects:

  • maternal folate status
  • maternal age

teratogenic medications and substances

maternal infections affecting the fetus

  • TORCH
    • Other infections: syphilis, varicella-zoster, parvovirus B19, zika virus
    • Rubella
    • Cytomegalovirus (CMV)
    • Herpes infections

premature births:

  • survival rates (RWH, Victoria, 2005):
    • < 23wks: rare - smallest surviving baby at RWH weighed 374g
    • 23wks: 67% (40% in 1997)
    • 24-25wks: 77% (73% in 1997)
    • 26-27wks: 82% with 1 in 5 having serious disability ?
    • 28-32wks: 98%   
    • term: 99% with 1 in 25 having serious disability
  • cutoff gestation for ICU care (costs $A2740 per day in 2005):
    • Holland 2005: 25-26wks or less
    • UK: under consideration by ethics committees 
    • Aust: no official cutoff but very unlikely a 22wk would get ICU care

parental age and pregnancy outcomes

maternal age < 20 years

  • overall risk of having a child with congenital anomalies is still relatively low, their fetuses may be predisposed to certain defects
  • gastroschisis
  • patent ductus arteriosis
  • pyloric stenosis
  • spina bifida
  • hydranecephaly
  • septo-optic dysplasia
  • optic nerve hypoplasia
  • anencephaly
  • cleft lip
  • polydactyly
  • schizencephaly

advancing maternal age

  • fertility declines with age:
    • one-third of women aged 35-39 and 50% of those over age 40 have fertility problems.
  • the incidence of pregnancy complications increases with maternal age:
    • hypertension
    • diabetes
    • premature births
    • stillbirths (overall risk not relative risk):
      • < 20 yrs: 0.5% risk
      • 20-30yrs: 0.4% risk
      • 35-39yrs: 0.5% risk
      • 40-44yrs: 0.65% risk
      • > 44yrs: 0.8% risk
    • twin pregnancy
  • the incidence of miscarriage increases:
    • < 25 yrs old: ~15% (9% if no prior aborts, ~20% if prior 1-2 aborts, 22% if prior > 2 aborts & parous, 50% if prior > 2 aborts & nulliparous)
    • 30 yrs old: ~ 18%
    • 35yrs old: ~23%
    • 40yrs old: ~35%
    • 45yrs old: ~60%
  • the incidence of birth defects increases with maternal age > 35 years:
    • trisomy 21 (Down's syndrome)
      • age 25 risk 1 in 1,250
      • age 30 risk 1 in 1,000
      • age 35 risk 1 in 400
      • age 40 risk 1 in 100
      • age 45 risk 1 in 30
    • congenital heart disease5):
      • laterality defects 2x risk
      • all conotruncal defects 1.3x risk
        • dextro-transposition of the great arteries 1.65x risk
        • coarctation of the aorta 1.5x risk
        • ventricular septal defects 1.2x risk
        • atrial septal defects 1.4x risk

young paternal age < 20 years

  • 1.1 x risk for low birthweight
  • increased neonatal and infant deaths
  • lower IQ

advancing paternal age

  • it is believed that DNA from the sperm cells of older fathers are more likely to develop CNVs than that from younger fathers.
    • CNVs are specific DNA mutations in which whole “chapters” of genetic material are either deleted or repeated.
  • age > 50 yrs doubles risk of autism and schizophrenia
    • paternal age appears to account for at least 25% of all schizophrenia
  • miscarriage rates
  • possibly decreased fertility
  • increased stillbirths
  • perhaps increased pre-eclampsia
  • 1.2x risk for low birth weight
  • bipolar depression
  • 1.09 x risk for each 10 year increment in paternal age for development of childhood brain cancer
  • lower IQ if age > 44
  • 2-3x higher childhood mortality

references:

  • Maternal age & fetal loss. Nybo Andersen et al. BMJ 2000; 320: 1708-12; (Denmark - 634272 women 1978-1992)
pregnancy.txt · Last modified: 2019/03/26 06:58 by gary1